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ACROMEGALY 


AN   ESSAY   TO  WHICH   WAS   AWARDED   THE   BOYLSTON 

PRIZE   OF   HARVARD   UNIVERSITY    FOR 

THE   YEAR    1898 


BY 

GUY  HINSDALE,  A.M.,  M.D., 

Fellow  of  the  College  of  Physicians  of  Philadelphia  and  of  the  American  Academy 
of  Medicine;   Member  of  the  American  Neurological  Association  and  Amer- 
ican Climatological  Association;   Assistant  Physician  to  the  Ortho- 
pedic  Hospital   and   Infirmary  for  Nervous   Diseases,  and 
to  the  Presbyterian  Hospital  in  Philadelphia,  etc. 


REPRINTED    FROM 

MEDICINE,  1898 

WII,I,IAM  M.  WARREN,  Publisher 
Detroit 


\N/. 


V  .—V 


Nulla  autem  est  alia  pro  certo  noscendi 
via,  nisi  quamplurimas  et  morborum  et 
dissectionum  historias,  turn  aliorum  turn 
proprias  collectas  habere,  et  inter  se  com- 
parare. 

MoRGAGNi,  Dc  Sed.  et  Cans.  Morb. 


DR.  WHARTON  SINKLER, 

WITH    THE    author's    high    REGARD   FOR    HIS    CONTRIBUTIONS 

TO  MEDICAL  I.ITERATURE  AND  FOR  HIS  QUALITIES 

AS    A    COLLEAGUE    AND    CONSULTANT. 


BOYLSTON   MEDICAL   PRIZES. 


These  prizes,  which  are  open  to  public  competition,  are  offered  annually 
for  the  best  dissertations  on  questions  in  medical  science  proposed  by  the 
Boylston  Medical  Committee. 

At  the  annual  meeting  in  Boston  in  1898,  a  prize  was  awarded  to  Guy 
Hinsdale,  M.D.,  of  Philadelphia,  Penn.,  for  an  essay  on  Acromegaly. 

For  1899  two  prizes  are  offered  :  — 

1.  A  prize  of  one  hundred  and  fifty  dollars  for  the  best  dissertation  on 
The  results  of  Original  Work  in  Anatomy,  Physiology,  or  Pathology. 
The  subject  to  be  chosen  by  the  writer. 

2.  A  prize  of  one  hundred  and  fifty  dollars  for  the  best  dissertation  on 
The  Results  of  Original  Investigations  in  the  Psychology  of  3Iental 
Disease. 

Dissertations  on  these  subjects  must  be  sent  post-paid  to  W.  F. 
Whitney,  M.D.,  Harvard  Medical  School,  Boston,  Mass.,  on  or  before 
January  1,  1899. 

For  1900  two  prizes  are  offered  :  — 

1.  A  prize  of  one  hundred  and  fifty  dollars  for  the  best  dissertation  on 
The  results  of  Original  Work  in  Anatomy,  Physiology  or  Pathology. 
The  subject  to  be  chosen  by  the  writer. 

2.  A  prize  of  one  hundred  and  fifty  dollars  for  the  best  dissertation  on 
The  method  of  Origin  of  Serpentine  Arteries  and  the  Structural  Changes 
to  he  found  in  them.  Their  Relation  to  Arterio-ca'pillary  Fibrosis, 
Obliterating  Endarteritis  and  to  Endarteritis  Deformans. 

Dissertations  on  these  subjects  must  be  sent  to  the  same  address  as 
above  on  or  before  January  1,  1900. 

In  awarding  these  prizes  preference  will  be  given  to  dissertations  which 
exhibit  original  work,  but  if  no  dissertation  is  considered  worthy  of  a 
prize,  the  award  may  be  withheld. 

Each  dissertation  must  bear  in  place  of  its  author's  name  some  sentence 
or  device,  and  must  be  accompanied  by  a  sealed  packet  bearing  the  same 
sentence  or  device,  and  containing  within  the  author's  name  and  residence. 
Any  clew  by  which  the  authorship  of  a  dissertation  is  made  known  to  the 
committee  will  debar  such  dissertation  from  competition. 

Dissertations  must  be  written  in  a  distinct  and  plain  hand,  and  their 
pages  must  be  bound  in  book  form. 

All  unsuccessful  dissertations  are  deposited  with  the  Secretary,  from 
whom  they  may  be  obtained,  with  the  sealed  packet  unopened,  if  called 
for  within  one  year  after  they  have  been  received. 

By  an  order  adopted  in  1826,  the  Secretary  was  directed  to  publish 
annually  the  following  votes  :  — 

1.  That  the  Board  do  not  consider  themselves  as  approving  the  doc- 
trines contained  in  any  of  the  dissertations  to  wliich  premiums  may  be 
adjudged. 

2.  That  in  case  of  publication  of  a  successful  dissertation,  the  author 
be  considered  as  bound  to  print  the  above  vote  in  connection  therewith. 

The  Boylston  Medical  Committee  is  appointed  by  the  President  and 
Fellows,  and  consists  of  the  following  physicians  :  Robert  T.  Edes, 
M.D.,  President ;  William  F.  Whitney,  M.D.,  Secretary ;  H.  P.  Bovr- 
DiTCH,  M.D.,  Frank  W.  Draper,  M.D.,  J.  Collins  Warren,  M.D., 
Samuel  G.  Webber,  M.D.,  F.  H.  Williams,  M.D.,  Edward  S.  Wood, 
M.D. 

The  address  of  the  Secretary  of  the  Boylston  Medical  Committee  is 
William  F.  Whitney,  M.D.,  Harvard  Medical  School,  Boston,  Mass. 


TABLE  OF  CONTENTS 


Page 

History  and  Definition i 

SymptomaToi<ogy 3 

Course  and  Duration 30 

Anatomy 31 

Pathology 35 

Etiology 43 

Theories  as  to  Acromegaly 45 

Gigantism 50 

Diagnosis 54 

Treatment 57 

Case  of  Acromegaly 66 

Skeleton  of  the  American  Giant .  69 

Bibliography 79 

Index ...  87 


ACROHEGALY:     AN     ESSAY     TO     WHICH     WAS     AWARDED     THE 

BOVLSTON   PRIZE  OF  HARVARD  UNIVERSITY 

FOR  THE  YEAR  1898. 

BY  GUY  HINSDALE,  A.M.,  M.D., 

Fellow  of  the  College  of  Physicians  of  Philadelphia  and  of  the  American  Academy  of  Medi- 
cine; Member  of  the  American  Neurological  Assoc'ation  and  American  Climato- 
logical  Association;    Assistant  Phy.sician  to  the  Orthopedic  Hospital 
and  Infirmary  for  Nervous  Diseases,  and  to  the  Presbyterian 
Hospital  in  Philadelphia,  etc. 

It  was  reserved  for  M.  Pierre  Marie,  about  ten  years  ago,  to 
recognize  the  identity  of  this  disease.  Isolated  cases  of  this  affection 
had,  no  doubt,  attracted  notice  all  over  the  world,  but  they  were 
regarded  as  peculiarities  of  an  individual,  as  an  example,  perhaps,  of 
local  hypertrophy;  or,  as  in  special  cases  warranting  clinical  descrip- 
tion, they  were  designated  under  the  names  of  macrosomia,  general 
progressive  hypertrophy,  prosopectasia,  general  hyperostosis,  anky- 
losis of  vertebral  column  with  deformation  of  bone;  or,  in  certain 
cases,  were  generally  recognized  as  giants.  Nevertheless,  in  1886, 
M.  Marie,  who  was  at  that  time  the  director  of  the  laboratory  in  La 
Salpetriere,  noticed  the  similarity  of  two  patients,  at  that  time  in 
the  wards.  A  study  of  these  cases  convinced  him  that  it  was  not  an 
accidental  resemblance,  but  the  outgrowth  of  a  pathologic  change, 
depending  upon  some  alteration  in  the  central  nervous  system.  He 
was  able  to  connect  the  manifestations  in  life  with  a  hypertrophy  of 
the  pituitary  body,  and  thus  gave  to  medical  nomenclature  a  new 
term.  Acromegaly,  or,  as  many  chose  to  call  it  in  honor  of  the 
observer,  ' '  Marie's  Malady,"  A  French  writer  calls  Marie  "  le  pere 
d' acromegalic." 

' '  Pachyacria ' '  has  been  proposed  by  Mosler  and  Arnold.  Prof. 
Cunningham,  and  Haughton  and  Ingram,  of  Dublin,  proposed  the 
name  ' '  megalacria, ' '  a  term  rationally  constructed  and  at  the  same 
time  euphonious.  It  is  probable,  however,  that  in  this  case,  as  in 
others,  custom  has  established  the  word,  and  it  will  remain  as  uni- 
versally adopted. 

The  name  is  derived  from  aupov,  a  summit  or  extremity,  and 
fxeya?  {fxkyaXi],  jxkyoc),  great.  The  name,  therefore,  designates  a 
condition  of  hypertrophy  or  unnatural  enlargement  of  the  extrem- 
ities of  the  body,  viz.,  the  hands,  feet,  fingers,  nose,  lower  jaw  and 
lips,  ears  and  cranium,  or,  as  Marie  designated  it,  "  une  hypertro- 
phic singuliere  non  congenitale  des  extremites  superieures,  infer- 
ieures  et  cephaliques. "  Von  Recklinghausen  proposes  the  term 
"  pachysemia." 


ACROMEGALY 


ACROMEGALY  3 

Syviptomatology .  —  The  first  symptom  which  usually  attracts 
attention  is  an  unaccountable  growth  of  the  hands,  and  shortly 
afterwards  of  the  feet.  Women  quickly  notice  the  necessity  for 
larger  and  larger  sizes  of  gloves.  I^arger  shoes  are  required;  in  some 
cases  the  sizes  needed  are  extraordinary,  reaching  as  high  as  No.  15 
in  the  usual  scale,  the  length  of  the  foot  attaining  twelve  inches. 

The  face  undergoes  corresponding  changes.  The  nose  broadens 
and  lengthens,  the  lower  lip  and  possibly  the  tongue  become  thick- 
ened and  protrude;  the  head  enlarges  and  the  features  become  so 
coarse  and  unlike  their  former  appearance  that  friends  notice  the 
marked  change,  or  fail  to  recognize  the  individual  after  an  absence. 

The  physician,  however,  is  usually  consulted  for  a  persistent 
headache  or  for  some  visual  defect,  and  in  this  way  many  of  the 
cases  have  presented  themselves  at  special  clinics.  In  not  a  few 
cases  they  have  been  "picked  off  the  street"  by  physicians  who, 
thanks  to  Marie,  have  come  to  be  familiar  with  the  characteristic 
features  of  a  disease  that  only  a  few  years  ago  they  allowed  to  pass 
unheeded. 

The  following  classification  of  symptoms  will  be  convenient  in 
considering  the  subject: 

I.  Objective  Symptoms. 
II.  Subjective  Symptoms. 

III.   General  Symptoms. 


Dr.  H.  H.  Vinke's  case,  aged  28  years. 


Same  patient,  aged  51  years;  fifteen  years  after 
onset  of  acromegaly. 


ACROMEGALY 


Fig.  3.— Skiagraph  of  right  hand;  case  of  acromegaly.    Dr.  Witmer's  case;  female,  aged  55. 


ACROMEGALY  5 

I.  Objective  Symptoms  (fundamental):  Hands;  fingers;  feet; 
toes;  head;  face;  nose;  lips;  tongue;  palate;  chin;  cranium;  trunk; 
spine;  thorax;  ribs;  sternum.  Objective  Symptoms  (accessory): 
Neck;  thyroid  body;  larynx;  thymus;  breasts;  abdomen;  genital 
organs;  circulatory  organs;  respiratory  organs;  muscles;  articula- 
tions; reflexes;  electrical  reactions;  skin  (sweat  glands);  urine; 
blood;  sensory  changes. 

II.  Subjective  Symptoms  (fundamental):  Headache;  amenor- 
rhea; sexual  desire;  vision;  thirst;  appetite.  Subjective  Symptoms 
(accessory):  Hearing;  smell;  taste;  cardiac  palpitation. 

III.  General  Symptoms:  Psychic  depression. 

OBJi;CTIV^   SYMPTOMS. 

Hands. — Among  the  first  symptoms  to  be  noted  by  the  patient  is 
an  increase  in  the  size  of  the  hands.  The  customary  gloves  are  dis- 
carded for  larger  and  larger  sizes,  and  in  not  a  few  cases  it  becomes 
necessary  to  have  special  gloves  made.  The  fingers  thicken  and  all 
the  tissues  seem  hypertrophied.  The  fingers  assume  a  shape  com- 
monly designated  as  "  sausage  -  shaped. "  Ordinary  rings  cannot 
be  worn.  One  of  Virchow's  patients  had  a  special  ring  made 
that  was  so  large  that  a  German  thaler  could  be  dropped  through 
it.  In  Roxburgh  and  Collis'  patient,  it  is  recorded  that  five 
times  over  she  required  to  have  her  rings  filed  off  her  fingers  and 
made  of  an  increased  size.  On  the  palmar  surface  of  the  hands, 
and,  for  that  matter,  upon  the  feet  as  well,  fleshy  pads  are  liable 
to  form.  The  epidermis  and  cutis  become  thickened,  and  the  whole 
hand  assumes  a  shape  which  is  denominated  "spade-like,"  or,  as 
the  French  term  it,  "  Main  en  battoir"  (battledore).  This  change 
in  the  hands  is  not  so  much  due  to  a  lengthening  of  the  member  as 
to  an  increase  in  circumference,  which  contrasts  quite  strongly  with 
the  unaltered  arm  and  forearm.  The  nails  are  commonly  flattened 
and  enlarged  and  may  be  striated  lengthwise.  Nodosities  have  been 
noted  about  the  phalanges. 

Feet. — The  feet  share  the  same  processes  as  are  noted  in  the 
hands,  and  their  increase  in  size  is  usually  coincident  with  the 
hypertrophy  in  the  upper  extremity.  Women  note  this  with 
dismay,  and  the  resulting  deformity  of  the  feet,  as  in  the  case 
of  the  hands,  leads  to  much  mental  disturbance.  The  spirits 
droop,  and  anxiety  on  this  account  leads  to  melancholy  and  a 
desire  for  seclusion.  The  toes  are  thickened  in  the  same  man- 
ner as  the  fingers. 


ACROMEGALY 


Fig.  4. — Dr.  Packard's  case  of  acromegaly  described  in  vol.  xvi  of  the  Transaclious  of  the  Col- 
lege of  Physicians  of  Philadelphia.  This  skiagraph  should  be  compared  with  the  picture  of 
Arnold's  case  in  Ziegler's  Pathology.  Hyperostosis  of  the  phalanges  is  well  shown.  Tlie 
entire  outline  of  the  ring  on  the  little  finger  is  plainly  seen.    Reduced. 


ACROMEGALY  7 

The  accompanying  illustration  shows  the  enormous  size  to  which 
the  feet  may  attain.  The  feet  of  this  patient,  who  was  i6  years 
old,  measured  36  centimeters  (14.25  inches);  the  width  was  16 
centimeters  (6.25  inches);  and  the  girth  of  the  first  toe  12.5 
centimeters  (5  inches). 

In  one  of  Dana's  cases,  a  young  giant,  the  feet  were  35.5  centi- 
meters (14  inches)  long  and  the  subject  wore  a  shoe  46  centimeters 
(18  inches)  in  length. 

A  tendency  to  fiat  feet  has  been  frequently  noted,  and  thick 
cushions  of  soft  tissues  may  surround  the  os  calcis  and  outer  border 
of  the  feet. 


Fig.  5. — James  W.  Walker's  case. 

Skiagraphs  of  the  enlarged  hands  and  feet  do  not  always  reveal 
hypertrophy  of  bone.  This  is  well  shown  in  Sir  WiUiam  Broad- 
bent's  case,  reported  in  1896.  The  patient  was  a  woman,  and  the 
bones  are  shown  to  be  of  normal  size,  the  hypertrophy  in  her  case 
residing  wholly  in  the  soft  parts. 

Head. — The  head  is  commonly  increased  in  size.  This  increase 
is  in  part  due  to  an  increase  in  the  capacity  of  the  sinuses,  or  the 
spaces  between  the  two  tables  of  the  skull.  This  is  quite  evident  in 
the  skull  of  the  case  described  by  the  author.  The  sinuses  are 
capacious,  although  the  tables  of  the  bone  are  not  elsewhere  enlarged. 
In  Regnault's  case,  however,  the  upper  portion  of  the  occipital  bone 
was  14  millimeters  in  thickness. 

The  forehead  is  commonly  low;  the  facial  bones,  with  the  excep- 
tion of  the  lower  maxillary,  do  not,  as  a  rule,  show  any  marked 


8  ACROMEGALY 

change.  This  bone,  in  a  large  proportion  of  cases,  is  the  seat 
of  characteristic  changes.  It  is  an  '' ocKpov,"  or  one  of  the 
extremities  of  the  body.  As  the  bone  hypertrophies  prognathism 
(cranium  progeneum)  ensues;  the  teeth  in  the  lower  jaw  may  pro- 
ject as  much  as  three  centimeters  (1.25  inch)  in  advance  of  the 
upper  teeth  (Regnault's  case).  This  is  well  seen  in  the  accompany- 
ing Figs.  6  and  7,  from  Professor  Osborne's  case,  in  which  a  com- 
plete study  of  the  skeleton  was  made.  In  the  130  cases  of  which 
we  have  made  a  synopsis,  prognathism  was  mentioned  as  present  in 
thirty-four.  The  changes  in  the  lower  jaw  are  commonly  attended 
with  a  loss  of  teeth.  Prognathism  is  the  resultant  of  the  growth  of 
the  body  of  the  inferior  maxilla,  an  increasing  obtuseness  of  its 
angle  and  changes  in  its  articular  surfaces. 

Nose. — This  is  one  of  the  principal  points  of  change.  The  nose 
becomes  broadened  and  in  many  cases  lengthened,  and  even  a  slight 
change  in  this  regard  makes  great  alterations  in  the  general  appear- 
ance. It  frequently  happens  that  the  expression  is  so  altered  that 
it  is  difficult  to  recognize  the  individual  after  these  changes  have 
occurred.  The  nose  flattens,  the  alae  thicken,  and  the  nostrils  are 
liable  to  be  enlarged.     The  septum  may  undergo  hypertrophy. 

Lips. — The  lips  are  commonly  thickened;  especially  is  this  true 
of  the  lower  lip,  which  may  be  greatly  everted. 

Tongue. — Occasionally  the  tongue  is  found  to  be  enlarged,  and 
this  may  be  a  source  of  considerable  inconvenience.     One  of  the 


Fig.  6. 


ACROMEGALY 


Normal  skull. 


Fig.  7. 
Skall  from  case  of  acromegaly  (Osborne) 


Fig.  8.— (i)  Distal  phalanx  of  toe;  (2)  normal  clavicle;  (3)  clavicle  from  case  of  acromegaly; 
(4)  normal  inferior  maxilla;  (5)  inferior  maxilla  from  case  of  acromegaly.     (Osborne.) 


lO 


ACROMEGALY 


Fig.  9.  Fig.  10. 

Jos.  S ,  aged  17.     Showing:   Eversion  of  the  lips;   prognathism  (5^  inch);   lower  jaw  large. 

Irregular  teeth;  high  palatal  arch;  narrow.  Deformity  of  the  head  with  frontal  prominence. 
Total  blindness,  probably  congenital.  Exophthalmus;  divergent  strabismus;  lateral  nys- 
agmus.     Mentality  good.     Case  shown  to  the  author  by  Dr.  F.  Savary  Pearce. 


Fig.  II. — Enlargement  of  the  nose  in  acromegaly  (Curschmann). 


early  cases,  that  of  Chalk,  was  described  in  1857  under  the  title  of 
"  Partial  lyuxation  of  the  I^ower  Jaw  Due  to  an  Enlarged  Tongue." 
In  our  collection  of  126  cases  the  tongue  has  been  noted  as  enlarged 
in  forty  instances.     The  tongue,  in  extreme  cases,  projects  from  the 


ACROMEGALY  ii 

mouth  and  interferes  with  distinct  articulation,  and  the  natural  tone 
of  the  voice  may  be  altered  by  changes  in  the  tonsils,  hard  and  soft 
palate,  and  fauces.  Even  in  women  the  voice  may  assume  a  deep 
tone,  and  is  variously  described  as  "harsh,"  "guttural"  (see  case 
of  Chauffard). 

Chin. — The  lengthening  of  the  chin  is  noticeable  in  the  majority 
of  cases.  This  tends  to  give  the  face  an  oval  contour.  The  prog- 
nathous chin  contributes  strongly  to  the  change  in  the  general 
appearance. 

Trunk.  — The  spine  undergoes  marked  alterations  as  the  disease 
advances.  One  of  the  commonest  symptoms  is  a  cervico  -  dorsal 
kyphosis.  The  head  tends  to  fall  forward  upon  the  chest  and,  as  in 
Mosse's  case,  the  bodily  stature  may  be  diminished.  In  the  skele- 
ton described  by  the  author,  it  is  estimated  that  the  height  would  be 
about  three  inches  greater  were  it  not  for  the  spinal  curvature 
present.  Kyphosis  is  due  to  changes  in  the  bodies  of  the  vertebral 
and  intervertebral  substances,  and  it  is  not  unusual  to  find  ankylosis 
or  a  bony  deposit  of  a  diffuse  character,  just  as  in  the  case  of  osteitis 
deformans  or  osteo-arthritis.  There  is  thus  produced  a  bridging  of 
the  superior  and  inferior  margins  of  the  vertebral  bodies,  due  to  the 
ossification  of  the  intervertebral  ligament.  Similar  changes  are 
observed  in  rickets  and  acromegaly;  they  are  liable  to  occur  as 
muscular  weakness  advances.  In  H.  Alexis  Thomson's  case  the 
sternum  and  ribs  were  of  gigantic  size,  but  none  of  the  measure- 
ments of  his  case  approach  the  measurements  seen  in  the  case  which 
we  describe. 

The  peculiar  deformity  due  to  kyphosis,  taken  in  connection 
with  enormous  hands  and  feet,  may  give  an  ape-like  appearance  to 
the  subject.     Lavielle's  case  is  a  good  example  of  this. 

These  changes  in  the  thorax  usually  make  the  antero-posterior 
diameter  greater  in  proportion  to  the  lateral.  The  sternum  and 
clavicles  share  in  the  hypertrophy.  The  abdomen,  in  well  marked 
cases,  is  prominent,  sometimes  pendulous  even  without  obesity; 
but  the  pelvis  is  not,  as  a  rule,  affected.  Where  the  kyphosis  is 
extreme,  the  iliac  crests  may  be  in  contact  with  the  lower  ribs. 
This  condition  is  sometimes  described  under  the  term  "Polichinelle" 
or  "  Polichinello,"  which  was  the  name  of  an  Italian  humpback  who 
was  famous  in  his  day. 

Lo7ig  Bones. — The  long  bones  are  not,  as  a  rule,  affected,  except- 
ing in  the  giant  form  of  acromegaly.  An  exception  to  this  rule 
was  recorded  by  lycslie  Thorne.  The  subject  was  a  man  of  48, 
in  whom  the  first  symptoms  had  appeared  at  the  age  of  21.     The 


12 


ACROMEGALY 


tibiae  and  fibulae  showed  a  marked  curve  outwards  and  forwards. 
The  long  bones  are  more  likely  to  show  changes,  if  at  all,  in  their 
extremities.     This  is  shown  very  well  in  Osborne's  case. 


^"•^^      -'^T^^BB 

i^^UHHH 

IRI^^^^^O 

1^ 

I^^^^mH 

^^^^^^Ihi^^k^^IIH 

^H^^hI 

1^^^ 

fl^^nl 

HBlHr 

^^m^  "^^g^^^^^^^^^^B 

'  .;^^^^^| 

■^^^B^PL'Ll^^  ^^jctImR^^^^^^^B 

, 

nl^^^^ra^^^^^^^l 

■■l^lll 

H^^^^^^l 

^^^^^^ 

'  '^-'"^^^^^^^^^B^^^B 

^\ 

^^B^^^jI^^^^  t^H^^^^^^^^^H 

,  ^mii^Bi^i 

Fig.  12. — Deformity  of  thorax  in  acromegalj-,  and  spinal  column  from  same  case  (Osborne). 

OBJKCTIVK   SYMPTOMS    (ACCESSORY). 

The  neck  is  hypertrophied.  We  have  found  this  noted  twenty- 
eight  times  in  our  collection  of  cases.  Tumors  in  the  neck,  entirely 
unconnected  with  the  thyroid,  have  been  observed  by  Henrot  and 
Dreschfeld.  In  the  latter  case  these  tumors  extended  into  the 
upper  part  of  the  thorax,  where,  to  judge  from  the  sternal  dulness, 
a  tumor  existed,  and  it  was  believed  took  its  origin  from  the  thymus 
gland.  The  nature  of  these  tumors  was  undetermined,  but  they 
were  believed  to  be  lympho-sarcomata,  and  it  has  been  noted  that 
growths  of  this  nature  sometimes  take  their  .starting-point  from  the 
remains  of  the  thymus  (Virchow-Koster).  These  growths  naturally 
give  rise  to  dyspnea. 


ACROMEGALY 


13 


Thyroid  Gland. — This  gland  has  been  found  to  be  either  uni- 
laterally hypertrophied  (Arnold),  generally  hypertrophied  (Bailey, 
Godlee,  Haskovec,  Pechadre,  Osborne,  Verstraeten,  Wolf,  Carpen- 
ter, Furnivall,  K.  J.  Smyth,  Henrot),  atrophied  (Erb,  Fratnich, 
Minkowski,  Haskovec,  Marie,  Curschmann,  Sigurini  and  Capor- 
iacco,  Tikhomiroff,  Linsmayer,  Somers),  atrophied  and  sclerosed 
(Bonardi),  absent  on  one  side  (Adler,  Waldo),  or  normal  (Freund, 
Hadden,  Ballance,  Comini,  D'Esterre,  Wadsworth,  Goldsmith,  Rol- 
leston,  Roxburgh  and  Collis,  Strzeminski,  Stroebe). 


Fig.  13. — Skeleton  of  an  acromegalic  (Fritsche,  Klebs,  and  Brigidi). 

Although  much  attention  has  been  paid  to  the  condition  of  the 
thyroid  in  acromegaly,  Dana  remarks:    "It  does  not  seem   to  me 


14 


ACROMEGALY 


Fig.  14. — Pendulous  abdomen  in  acromegaU'  (Curschmann). 


ACROMEGALY  15 

that  there  is  any  evidence  whatever  that  this  gland  has  a  relation 
to  acromegaly."  We  cannot,  however,  dismiss  the  subject  so  sum- 
marily. The  tendency  is  to  ascribe  considerable  importance  to  the 
thyroid.  Those  who  maintain  that  a  relationship  of  importance 
exists  are  Erb,  Gauthier,  Haskovec,  Chealde,  I^annois,  Murray, 
Rogowitsch,  Stieda,  J.  J.  Putnam, ^  Wells. 

Five  cases  of  acromegaly  are  on  record  in  which  exophthalmic 
goitre  coexisted.  In  another  case  an  "extra-thyroid"  gland  was 
found  by  Osborne  "in  the  median  line  high  up  in  the  chest  cavity 
just  above  the  upper  end  of  the  sternum."  It  contained  "a  large 
amount  of  iodine. ' ' 

We  think  it  very  significant  that  in  one  case,  at  least,  of  myxe- 
dema the  hypophysis  has  been  found  hypertrophied.  This  was  in  a 
case  reported  by  Gron  in  1894.  It  occurred  in  a  woman  of  62.  The 
thyroid  was  atrophied,  and  at  the  autopsy  the  enlarged  hypophysis 
occupied  the  entire  sella  turcica  and  was  said  to  be  "  as  large  as  a 
nut."  It  seems  probable  that  this  case  was  an  example  of  compen- 
satory hypertrophy.  We  believe  that  future  investigations  will 
doubtless  establish  a  distinct  relation  between  these  glands. 

Zarj/72X.— The  larynx  shares  in  the  hypertrophy  of  the  neck. 
Even  in  a  woman  the  cartilages  become  prominent  in  a  few  cases, 
and  the  tone  of  the  voice  grows  deeper,  or  at  least  harsh,  difficult,  or 
naso- guttural.  This  change  in  voice  is  due  partly  to  alterations  in 
the  cartilages  and  vocal  cords,  and  partly  to  changes  in  the  form 
and  size  of  the  antrum  or  other  resonant  cavities  in  the  face.  We 
have  noted  alterations  in  the  larynx  in  eighteen  cases.  In  a  case 
recorded  by  Chappell  the  epiglottis  was  thickened,  the  arytenoid 
cartilages  and  the  ventricular  bands  were  enlarged,  but  the  glottic 
aperture  was  very  small.  The  pillars  of  the  fauces,  soft  palate  and 
uvula  were  thickened,  and  the  tonsils  and  lingual  glands  were 
hypertrophied.  While  quiet  respiration  was  free,  but  during  excite- 
ment, labored.     The  patient  died  during  an  attack  of  dyspnea. 

Thymus  Gla7id.—'T\i&  thymus  gland  has  been  supposed  to  play  a 
prominent  role  in  acromegaly.  This  opinion  was  first  prominently 
enunciated  by  Erb,  who  laid  great  stress  on  hypertrophy  of  the 
gland,  as  revealed  by  dulness  on  percussion  over  the  upper  sternum. 
Schultze  and  Verstraeten  have  supported  Erb  in  his  belief  as  to  the 
persistence  of  the  thymus  in  acromegaly.  "  Erb's  sign,"  as  it  is 
called,  is  rather  uncommon  in  acromegaly.     It  has,  however,  been 

1  "Acromegalia  probably  stands  as  near  to  myxoedema  and  diseases  of  the  thyroid  or 
kindred  organs  as  Graves's  disease,  if,  indeed,  the  bond  be  not  closer."— Trans.  Assoc'n 
Amer.  Phys.,  1893;  paper  on  cases  of  myxedema,  acromegalia,  etc. 


1 6  ACROMEGALY 

noted  post-mortem  by  Arnold,  Klebs,  Dalton,  Lathuraz,  Mosse, 
Holsti,  Rolleston,  Ross,  Roxburgh,  and  Collis,  and  clinically  by 
Erb,  Dreschfeld,  Caton,  Campbell,  Bertrand,  Flemming. 

In  Mosse' s  case,  the  post-mortem  examination  revealed  an  enor- 
mous growth  or  ' '  revivescence ' '  of  the  thymus.  It  extended  in  front 
of  the  trachea,  from  the  thyroid  gland  to  the  pericardium,  measuring 
twelve  to  thirteen  centimeters  vertically  and  eight  centimeters  trans- 
versely. 

MammcB. — The  breasts  are  occasionally  atrophied. 

Genital  Organs.  —  The  external  organs  may  be  hypertrophied, 
while  the  uterus  and  testicles  are  found  to  be  atrophied.  It  is  a 
common  thing  to  find  that  menstruation  has  ceased  at  the  onset 
of  the  disease.  In  the  giant  form  of  acromegaly,  as  well  as  in 
the  ordinary  form,  sterility  is  the  ordinary  condition. 

Circulatory  Organs. — These,  as  a  rule,  are  only  slightly  affected, 
or,  at  least,  little  note  has  been  made  as  to  any  changes  in  them, 
J.  B.  C.  Fournier,  however,  has  made  a  careful  study  of  the  heart 
in  acromegaly,  and  has  noted  two  forms  of  cardiac  alteration:  (i)  A 
pure  hypertrophy  without  degenerative  lesion  of  the  muscular  fiber; 
this  is  generally  the  condition  noted  at  autopsies.  (2)  A  hyper- 
trophy accompanied  by  cardiac  sclerosis  with  degeneration  of  mus- 
cular fiber. 

In  the  first  instance  there  is  a  simple  cardiomegaly  accompanied 
exceptionally  with  insufficiency  of  the  cardiac  valves.  In  the  second 
there  is  a  true  sclerotic  myocarditis,  a  cardio-renal  arteriosclerosis 
with  what  he  terms  a  hypo-systole,  a  cardiac  liver  with  edema  of 
the  feet,  and  albumen  in  the  urine.  Thus  the  heart  participates 
in  the  general  growth.  In  Osborne's  case  it  weighed  thirty -nine 
ounces. 

Tachycardia  has  been  observed  by  Ballard,  Boltz,  J,  J.  Putnam, 
du  Cazal.     Attacks  of  palpitation  are  occasionally  noted. 

The  arteries  share  the  fibroid  change,  becoming  rigid,  and  the 
veins  distend,  especially  in  the  lower  extremities.  Varicose  veins 
are  quite  commonly  observed. 

The  lesions  of  the  vascular  system  present  three  phases — dilata- 
tion of  the  vessels,  thickening  of  the  walls,  and  obliteration  of  their 
lumen.  So  in  the  subcutaneous  cellular  tissue  the  vessels  have  their 
walls  thickened,  especially  as  regards  the  muscular  coat;  the  inner 
coat  is  slightly  thickened  and  not  in  all  the  vessels. 

The  Respiratory  Organs.  —  These  are  not  liable  to  be  affected 
unless  changes  occur  in  the  thyroid  and  thymus  glands.  The 
movements  of  respiration  in  aggravated  cases  are  more  abdominal 


ACROMEGALY 


17 


Fig.  15. — Varicose  veins  in  acromegaly.    Case  shown  to  the  author  bj-  Dr.  A.  A.  Eshner. 


1 8  ACROMEGALY 

than  thoracic;  the  upper  thorax  may  be  rigid  and  the  spinal  curva- 
ture may  throw  the  thorax  forward  on  the  pelvis,  as  has  been 
previously  mentioned. 

Muscles. — The  muscular  system  varies  in  development  with  the 
type  and  stage  of  the  disease.  Naturally,  the  strength  is  great  in 
the  early  period  and  particularly  in  the  giant  form.  Virchow's 
patient  is  reported  to  have  been  able  to  lift  800  pounds;  Eshner's 
case  is  that  of  a  blacksmith  in  vigorous  health,  still  following  his 
arduous  occupation.  The  fact  that  the  disease  has  existed  for  a 
considerable  time  when  the  cases  are  reported,  and  that  they  apply 
to  physicians  for  relief  of  symptoms,  explains  why  muscular  power 
is  commonly  noted  weak  as  a  rule.  The  muscles  are  not  nearly  so 
well  developed  as  the  measurements  of  the  members  would  imply. 
The  hypertrophy  affects  all  the  tissues,  and  muscular  action  is  more 
likely  to  be  impeded  than  facilitated.  As  a  rule,  the  forearm 
remains  unaffected,  while  the  tissues  of  the  hand  increase  in  bulk. 
As  the  period  of  decadence  sets  in,  muscular  atrophy  renders  the 
patient  quite  powerless,  and  cardiac  dilatation  adds  to  the  weakness 
of  the  circulation.     Tremor  is  not  unusual  in  acromegaly. 

JoiJits. — The  articulations  are  to  some  extent  involved.  This 
applies  to  the  wrists,  the  smaller  joints  of  the  hands  and  feet.  The 
changes  in  the  intervertebral  joints  have  already  been  referred  to. 

Reflexes. — These  are  generally  preserved.  In  Stembo's  and 
Osborne's  cases  the  knee-jerk  was  absent  on  the  right  side  and 
diminished  on  the  left.  It  was  absent  in  the  cases  of  Remington, 
Pinel-Maisonneuve,  Mendel,  Claus,  Banks,  Marie,  Pechadre, 
Flemming;  nearly  absent  in  Bertrand's  case;  weak  and  only 
obtained  by  reenforcement  in  the  cases  of  Pick;  weak  in  Masso- 
longo's  case,  also  in  Hertel's,  Dana's,  Dercum's,  Bignami's,  Bar- 
clay and  Symmes' ,  Strzeminski's,  Schultze's,  Adler's,  Haskovec's, 
Church's,  and  Hassert's;  increased  in  the  case  of  Pershing.  In 
Marinesco's  case  it  was  normal  in  the  left,  but  exaggerated  and  with 
clonus  in  the  right.  Thus  in  twenty -four  cases,  or  19  per  cent., 
there  was  some  change  noted  regarding  the  knee-jerks.  The 
remaining  102  cases,  as  far  as  reported,  were  normal  in  this  respect. 

Electrical  Reactions.  —  Conductivity  to  the  electric  current  is 
increased,  owing  to  diminution  of  the  electric  resistance.  As  the 
current  is  more  readily  conveyed  by  the  blood-current  than  by  other 
tissues,  this  would  be  the  natural  result.  In  this  case,  where  the 
vessels  themselves  are  enlarged,  the  resistance  is  much  less  than 
where  the  fluid  is  merely  contained  in  the  cellular  tissue,  as  in 
edema.     In  the  latter  case  there  is  no  appreciable  change  in  the 


ACROMEGALY 


19 


Fig.  16. — Skiagraph  of  right  forearm  and  wrist  from  case  of  acromegaly  (Osborne). 


20  ACROMEGALY 

conductivity  of  the  electric  current.  We  have,  then,  every  reason 
to  expect  in  acromegaly  a  lessening  of  the  electrical  resistance  as 
one  of  the  symptoms.  This  has  been  denominated  the  "Charcot- 
Vigouroux"  sign,  and  is  present  in  exophthalmic  goitre,  in  which, 
of  course,  the  vessels  are  vv^idely  dilated. 

Ski7i,  Nails,  and  Hair. — These  tissues  undergo  corresponding 
changes.  In  some  cases  the  skin  of  the  scalp  is  hypertrophied. 
The  skin  of  the  face  is  thickened  and  may  be  yellowish  or  sallow. 
Both  the  cutis  and  epidermis  are  thickened,  the  sudorific  glands 
hypertrophy,  and  the  pigment  of  the  rete  malpighii  becomes 
excessive. 

The  general  hue  of  the  skin  in  advanced  cases  has  given  rise  to 
the  term  employed  by  Gauthier,  "  cachexic  acromegalique."  It  is 
not  unusual  to  find  reddish,  pedunculated  warts  and  mollusca  fibrosa 
in  acromegaly.  The  latter  excrescences  are  quite  commonly  noted, 
and  their  presence  has  come  to  be  one  of  the  corroborative  signs  of 
the  disease.  The  skin  of  the  hands  and  feet  may  assume  the  char- 
acter of  coarse  pads  or  folds.  The  hands  are,  therefore,  of  hard 
consistence,  without  pitting  on  pressure,  as  in  edema. 

The  hair  of  the  head  may  be  coarse,  and  the  nails  may  undergo 
striation  either  laterally  or  longitudinally;  they  may  be  short  and 
flat  and  small  in  comparison  with  the  hypertrophied  fingers.  The 
perspiration  may  be  excessive  and  even  offensive. 

Acromegaly  is  thus  entitled  to  a  place  among  the  dystrophies. 

Uriyie. — The  urine  is  commonly  augmented  in  quantity.  It  is 
not  unusual  for  a  man  having  acromegaly  to  pass  from  2000  to 
3000  cubic  centimeters  daily.  Pick's  case  passed  4000  cubic  centi- 
meters, Marinesco's  10,000  to  12,000  cubic  centimeters,  Walker's 
12,600  cubic  centimeters,  in  twenty- four  hours. 

Other  cases  where  the  urine  was  increased  are  those  of  Balzer, 
Banks,  Barclay  and  Symmes,  and  Hanseman.  This  was  also- 
observed  in  the  cases  of  Caton,  Claus,  Gordinier,  Marinesco,  and 
Moncorvo. 

The  urine  often  contains  sugar.  In  the  latter  case  the  urine 
varies  from  1036  to  1040  in  specific  gravity  and  contains  6.25  per 
cent,  of  sugar.  In  Ross's  case  the  specific  gravity  was  1045.  In 
Marinesco's  case  there  was  forty-eight  grammes  of  sugar  per  liter. 

Cases  of  glycosuria  are  recorded  by  Ballard,  Brooks,  Dalton, 
Dallemagne,  Gajkiewicz,  Gonzales- Cepeda,  Marinesco,  Ross,  Striim- 
pell,  Squance,  Walker,  Thomson,  Hanseman,  and  Lathuraz. 

Albumen  was  noted  in  the  cases  of  Ballard,  Caton,  S.  Solis- 
Cohen,  Arnold,  Gauthier,  Marinesco,  Gajkiewicz,  Dreschfeld. 

Azoturia  and  phosphaturia  may  also  be  present. 


ACROMEGALY  21 

Scanty  urine  has  been  noted  by  Bramwell  twice,  and  by  Hare. 

The  urine  was  normal  in  29  out  of  the  130  cases  in  our  appendix. 

Blood. — Changes  have  been  observed  in  the  few  cases  in  which 
the  condition  of  the  blood  has  been  examined  and  recorded.  In 
Church  and  Hassert's  case  the  hemoglobin  reached  95  per  cent,  and 
the  red  corpuscles  7,000,000  per  cubic  millimeter.  There  were  400 
red  to  one  white  corpuscle.  In  three  cases  of  Marie  and  Marinesco 
the  red  corpuscles  and  the  hemoglobin  were  both  diminished.  The 
blood  of  one  of  these  patients  was  also  examined  by  M.  Lion  in 
Professor  Hayem's  laboratory  with  similar  result.  Marie  and 
Marinesco  have  also  made  the  following  statement:  "Hyperplasia 
of  the  bone-marrow  plays  a  part  in  this  leucocytosis,  because,  at  the 
same  time,  there  were  red  corpuscles  and  eosinophile  cells  in  larger 
quantity  than  normal." 

Sensation. — Few  changes  in  this  regard  have  been  noted.  One 
of  Marinesco' s  cases  had  normal  tactile  sensation  in  the  left  leg,  but 
diminished  in  the  right.  In  Chauffard's  case  there  was  a  hysterical 
left  hemianesthesia.  Hypersensitiveness  to  cold  was  noted  by  Per- 
shing and  Gordinier.  In  Caton's  case  there  was  hyperesthesia  over 
the  left  lower  maxilla,  and  in  Claus'  case  the  tactile  sense  was  noted 
as  being  acute.  Subjective  sensations  are  occasionally  noted.  Orsi's 
case  complained  of  a  sense  of  burning  in  the  face.  Haskovec's 
patient  had  regularly  a  sense  of  heat  followed  by  great  perspiration, 
succeeded  by  a  sense  of  cold. 

Temperature. — Verstraeten  and  Gauthier  have  noted  a  very 
slight  difference  between  the  axillary  temperature  and  that  in  the 
palm  of  the  hand.  In  Gauthier' s  case  it  was  36.5°  in  the  axilla; 
36.2°  in  the  palm.  The  usual  difference  normally  is  2°  or  3°  C. 
This  is  simply  an  indication  of  the  excessive  blood-supply  of  the 
extremities,  a  condition  likely  to  give  rise  to  hypertrophy  of  bone. 
Subnormal  temperature  was  found  in  Waldo's  case. 

SUBJECTIVE   SYMPTOMS    (FUNDAMENTAI.). 

Headache.  —  This  is  one  of  the  commonest  complaints  of  the 
acromegalic.  It  is  the  direct  product  of  the  intracranial  growth 
which  is  seated  in  the  pituitary  fossa.  By  its  presence  and  its  pres- 
sure on  the  optic  nerves  and  the  base  of  the  brain  this  symptom 
becomes  one  of  the  cardinal  signs  of  the  disease.  The  anatomical 
relations  of  the  hypophysis  cerebri  will  be  considered  in  another 
chapter. 

Headache  may  be  so  persistent  and  severe  as  to  affect  the  gen- 
eral disposition  of   the   sufferer.      The   spirits   are   depressed   and 


22  ACROMEGALY 

suicide  has  even  been  threatened,  and  carried  out  on  account  of  the 
desperate  condition  of  the  patient  (Pick).  It  may  be  constant  or 
intermittent,  and  may  be  locaHzed  in  the  occiput,  the  frontal  region, 
or  confined  to  one-half  of  the  head. 

The  duration  of  this  symptom  was,  in  Gauthier's  case,  twenty- 
nine  years,  and  in  Gonzales- Cepeda's  case  it  was  described  as 
intense.  In  both  of  these  the  autopsy  showed  large  growths  of  the 
hypophysis  which  amplj^  explained  the  symptom.  In  Gajkiewicz's 
case  the  patient  was  described  as  groaning  and  lamenting  for  two 
years  with  headache.  In  Barclay  and  Symraes'  case  the  duration 
was  five  years;  in  Ross's,  three  years,  confined  to  the  left  temple. 
In  one  of  Marinesco'  cases  it  had  lasted  four  years,  and  in  another 
was  seven  in  the  occiput,  while  a  third  was  confined  to  the  temples. 
In  Sanger  Brown's  case  it  was  frontal;  in  Campbell's  it  was  located 
in  the  eyeballs  and  head;  in  Caton's  it  seemed  to  be  situated  at  the 
base  of  the  skull. 

Other  cases  where  headache  was  a  sj^mptom  are  those  of  Banks, 
Barrs,  Bertrand,  Chauffard,  Claus,  two  cases  of  S.  Solis-Cohen  (in 
one  having  lasted  for  seven  or  eight  years),  Dana,  Dreschfeld, 
Eshner,  Guinon,  Goldsmith,  Haskovec,  Lavielle,  Long,  Massolongo, 
Mendell,  Middleton,  Olechnowicz,  Orsi,  Osborne,  Packard,  Parsons, 
Pechadre,  Pershing,  Phillips,  Pick,  Pinel,  Ross,  RoUeston,  Schlesin- 
ger,  Lynn  Thomas,  and  Thomas  of  Geneva,  Unverricht,  and  Whyte. 

Intense  neuralgia  of  the  cranial  nerves  has  called  for  surgical 
interference.  Prominent  among  these  is  the  case  of  Hare,  which 
was  operated  upon  by  Keen  (see  under  "Treatment"),  and  the 
case  of  Caton.  Harris,  Squance,  Walker,  Fratnich  and  Godlee 
have  also  recorded  instances  of  severe  neuralgia  in  acromegaly. 

Amenorrhea. — This  has  already  been  referred  to  under  the  head- 
ing of  "  Genital  Organs." 

Sexual  Desire. — Pari  passic  with  the  atrophy  of  the  uterus  and 
testicles,  sexual  power  and  desire  abate,  and  as  the  disease  advances 
are  lost  altogether. 

Ocular  Symptoms. — The  appendages  of  the  eye  are  liable  to  be 
involved  early.  The  bones  and  orbital  ridges  are  heavy;  the  car- 
tilages and  skin  of  the  lids  thicken  by  reason  of  a  hypertrophy  of 
the  lowest  layer  of  the  true  skin  and  of  the  connective  tissue  and 
gland  of  the  skin.  The  secretion  of  tears  is  occasionally  augmented. 
The  pigment  may  be  increased  and  the  general  color  of  the  lids  may 
be  like  bronze.  The  globes  themselves  are  prominent,  constituting 
an  exophthalmus  which  has  been  so  extreme  as  to  occasion  a  true 
luxation  of  the  eyeball  (Hertel).     In  the  cases  of  Motais  and  Pinel- 


ACROMEGALY  23 

Maisonneuve,  it  is  said  that  one  could  see  the  entire  globe  as  far  as 
the  posterior  pole. 

We  find  exophthalmus  recorded  in  23  out  of  130  cases,  or  17.5 
per  cent.  (Cases  of  Banks,  Ballard,  Benson,  Bignami,  Bullard, 
Brooks,  Flemming,  Gauthier,  Guinon,  Hare,  Harris,  Minkowski, 
Godlee,'  Hertel,  ^losse,  Motais,  Orsi,  Pinel-Maisonneuve,  Striimpell, 
Thomas,  Valat,  Sigurini,  and  Caporiacco;    see  also  case  of  Joseph 

S ,  Figs.  9  and  10.) 

Exophthalmus  probabl}'  occurs  by  reason  of  a  proliferation  of 
the  adipose  tissue  back  of  the  bulb.  One  case  was  recorded  by 
Burchard  in  which  the  eyeball  itself  was  enlarged.  The  movements 
of  the  eyes  may  be  slow,  with  a  failure  to  raise  the  lids  synchro- 
nously. 

Nystagmus  has  been  obser\^ed  by  Bignami,  Boltz,  Long,  ^laison- 
neuve,  Packard,  Whyte,  Moncorvo,  Schlesinger,  and  Striimpell.  It 
may  be  either  spastic  or  ataxic. 

Internal  strabismus  has  been  observed  by  Banks,  Benson,  Camp- 
bell, Godlee,  Moncorvo,  and  Lynn  Thomas.  Strabismus  divergens 
has 'been  recorded  by  Striimpell,  Franke,  Hertel,  Litthauer,  Mari- 
nesco,  and  Valat;  of  the  right  eye  alone,  by  Bignami;  and  of  the 
left  eye,  by  Spillman  and  Haushalter,  Schlesinger  and  Marinesco. 
Thus  there  may  be  a  complete  oculo- motor  paralysis  (third 
nerve)  and  occasionally  partial  paralysis  of  the  sixth.  Diplopia 
may  therefore  be  observed  as  a  result  of  ocular  paralysis.  The 
irides  sometimes  react  slowly  to  light,  but  normally  to  accommoda- 
tion. 

In  Lynn  Thomas'  case  the  left  iris  did  not  react  when  a  jet^  ot 
light  was  thrown  into  the  insensitive  half  of  the  left  retina,  it  being 
a^'case  of  left  temporal  hemianopsia.  But  both  pupils  contracted 
when  the  light  was  focused  on  the  sensitive  portion  of  the  retina 
(Wernicke's  reaction). 

Vision.— "t\i\s  has  been  recorded  as  normal  in  the  cases  of  Apple- 
yard,  Barrs,  Bertrand,  S.  Brown,  Claus,  Solis-Cohen,  Dallemagne, 
Dana,  Eshner,  Fratnich,  Gauthier,  Gerhardt,  Godlee,  Gordinier  (2), 
Guinon,  Mosse,  Osborne,  Pick,  Remington,  Shiach,  Squance, 
Thomas,  Thomson  and  Waldo,  Adler,   Dalton. 

Vision  is  impaired  in  the  majority  of  cases.  In  our  analysis  of 
130  cases,  we  have  found  some  note  as  to  defect  of  vision  in  about 
61 ,  or  48  per  cent.  It  is  quite  likely  that  the  proportion  of  cases  of 
defective  vision  is  much  greater  than  these  figures  would  imply, 
inasmuch  as  all  cases  are  not  studied  with  equal  care  in  this  respect. 
The  visual  acuity  may  vary  from  normal  to  a  slight  amblyopia  or 


24  ACROMEGALY 

even  complete  amaurosis,  in  which  there  may  be  either  congestion 
of  the  optic  nerves  or  neuro-retinitis  with  complete  atrophy  of  the 
nerves.  The  form  fields,  and  sometimes  the  color  fields,  are  very 
commonly  restricted.  This  condition  may  be  an  irregular  narrow- 
ing of  the  visual  fields  or  a  clear-cut  temporal  or,  rarely,  a  nasal 
hemianopsia  (case  of  Bard). 

Bitemporal  hemianopsia  is  due  to  a  blindness  of  the  nasal  half  of 
each  retina,  causing  a  loss  of  the  temporal  half  of  each  field.  This 
symptom,  as  we  shall  see  later,  is  caused  by  an  overgrowth  or 
neoplasm  of  the  hypophysis  pressing  on  the  optic  nerves  and  by 
bony  changes  in  the  optic  foramina  consequent  on  the  abnormal 
growth  of  the  lesser  wing  of  the  sphenoid  bone.  In  this  manner  the 
arterial  supply  of  the  nerve  and  eyeball  is  disturbed. 

Complete  homonymous  hemianopsia  has  been  observed  by  Ross 
and  also  by  Sir  W.  H.  Broadbent,  and  was  considered  to  be  due  to  a 
tumor  of  the  pituitary  body  pressing  on  the  right  optic  tract.  Left 
homonymous  hemianopsia  was  seen  by  Dodgson,  and  was  also 
recorded  by  Dulles,  in  the  latter  case  the  examination  having  been 
made  by  De  Schweinitz. 

An  example  of  ocular  changes  in  acromegaly  is  seen  in  a  case 
recorded  by  M.  Arthur  Benson.  The  patient,  a  farmer  of  38,  first 
sought  medical  advice  for  failing  vision.  It  w^as  found  that  he  had 
a  central  scotoma  for  colors  and  probably  hemianopsia  for  color. 
These  symptoms  almost  entirely  subsided  under  the  use  of  iodide  of 
potassium  and  the  cessation  of  tobacco.  Two  years  later,  however, 
when  the  use  of  tobacco  was  resumed,  vision  was  totally  lost;  but 
gradually  it  w^as  completely  restored  under  the  use  of  fresh  thyroid 
extract,  twenty -five  minims  three  times  a  da5^  There  remained, 
however,  a  slight  defect  in  the  upper  temporal  quadrant  of  the  field 
in  each  eye — tetranopsia.  The  changes  in  this  case  were  therefore 
largely  of  a  toxic  character. 

More  typical  cases  of  ocular  disturbance  are  those  recorded  by 
Strzeminski. 

The  visual  disturbances  are  among  the  early  signs  and  usually 
take  a  progressive  course.  In  one  of  Schultze's  cases  the  first 
symptoms  of  visual  trouble  had  existed  for  ten  years,  and  during  the 
last  half  of  this  period  there  had  been  complete  temporal  hemian- 
opsia. In  Long's  case  blindness  had  existed  for  ten  years,  com- 
mencing at  the  age  of  38.  Complete  blindness  has  occurred  within 
two  or  three  3'ears  from  the  onset  of  the  ocular  symptoms. 

Bitemporal  hemianopsia  has  been  noted  by  Benson,  Boltz,  Bram- 
well,  Sanger,   Brown,  Co  well,  S.  Solis- Cohen,  Curschmann,  Flem- 


ACROMEGALY  25 

ming,  Franke,  Gajkiewicz  (2),  Hertel,  Marinesco,  D'Esterre, 
Mendel,  Packard,  Schlesinger  (2),  Steinhaus,  Strzeminski,  Scliultze, 
Unverricht,  and  Valat. 


-ISO       C 


tAxii  3e».  15^74 


ToAv.-j,  /?qi. 


L 

Fig.  17.— Fields  from  a  case  examined  by  Doyne. 

Temporal  hemianopsia  of  the  right  side  is  recorded  by  Banks, 
Bramwell,  Church  and  Hassert,  also  Mosse;  of  the  left  side  by 
Caton,  Dercum,  Hare,  Pershing,  Striimpell.  Nasal  hemianopsia 
on  the  right  by  Roxburgh  and  Collis  (see  appendix). 

The  ophthalmoscope  shows,  in  the  early  stages,  a  venous  con- 
gestion; later  on,  a  papillitis.  In  a  case,  as,  for  instance,  that  of 
Benson,  we  find  the  nerve  paler  than  normal  with  evidences  of  past 
perivasculitis,  while  in  Pel's  case  there  was  choked  disk  of  such  pro- 
nounced type  that  the  diagnosis  of  brain  tumor  was  made  from  the 


26 


ACROMEGALY 


ocular  examination.  The  condition  is,  however,  a  rare  one,  and  its 
rarity  is  explained  by  Rask  as  due  to  a  very  marked  agglutination 
of  the  optic  nerve  fibers  under  the  pressure  of  the  pituitary  body, 
cutting  off  the  communication  of  the  intervaginal  space  of  the  nerve 
with  the  subarachnoid  space  of  the  brain,  this  communication  being 
supposed  necessary  to  produce  choked  disk. 

Optic  Atrophy. — This  is,  naturall}^,  consecutive  upon  the  pressure 
symptoms.  Whenever,  as  we  have  learned  from  cases  that  have 
been  examined  post  mortem,  the  optic  nerves  have  been  flattened 
by  contact  with  the  ever  -  expanding  hj'pophysis,  the  microscopic 
examination  will  show  a  degeneration  of  the  nerve  fibers.  The 
clinical  symptom  will  therefore  be,  on  ophthalmoscopic  examina- 
tion, a  progressive  atrophy  of  the  optic  nerve. 

An  observation  recently  made  by  Strzeminski  (1897)  shows  us 
that  in  the  cases  of  atrophy  that  are  not  preceded  by  temporal  hemi- 
anopsia we  must  suppose  that  the  gland  considerably  hypertrophied, 
and  exerts  from  the  start  a  pressure  upon  the  nerves  m  toto. 

Optic  atrophy  has  been  recorded  by  Bignami,  Bramwell,  Camp- 
bell, Caton,  Chauffard,  Cowell,  Dallemagne,  Denti,  Dreschfeld, 
Costanzo,  Flemming,  Graham  (2),  Hadden  and  Ballance,  Hare, 
Long,    Massalongo,    Packard,     Rolleston,     Roxburgh    and    Collis, 


Fig.  18. 


I'ershinar's  case. 


Fig.  19. 


ACROMEGALY  27 

Schlesinger  (2),  Steinhaus,  Surmont,  Unverricht,  Valat,  Walker, 
Strzeminski. 

How  far  the  changes  in  the  optic  nerves  are  due  to  bony  changes 
in  the  base  of  the  skull  has  given  rise  to  some  discussion.  It  is 
probable,  as  Broca  believes,  that  there  may  be  some  narrowing 
of  the  optic  foramina  from  this  cause;  but  evidence  on  this  point 
is  not  at  hand. 

Pains  in  the  eyeball  of  a  neuralgic  type  are  recorded  by  Erb, 
I^ombroso,  Hare,  Tanzi,  Striimpell. 

77„>^/._ Patients  sometimes  have  an  inordinate  thirst,  a  demand 
for  fluid  out  of  all  proportion  to  even  the  extraordinary  size  of  some 
of  the  subjects.  Remington's  patient  could  drink  a  gallon  of  beer 
at  once;  but  he  was  a  large  man,  six  feet  two  inches  in  height,  and 
weighed  268  pounds.  One  of  the  cases  which  we  record  could  drink 
three  or  four  quarts  of  milk  at  once.  We  find  a  memorandum  of  17 
patients  among  130  in  whom  polydipsia  was  a  symptom.  Increased 
thirst  is  doubtless  connected  with  the  glycosuria  present  in  many  of 

these  cases. 

Appetite.— 't\i\s  is  increased  more  frequently  than  thirst  and  is 
recorded  in  twenty  -  five  cases.  This  symptom  may  exist  without 
increased  thirst,  and  vice  versa.  In  one  case  it  was  noted  that  eating 
gave  great  relief  to  the  general  discomfort  of  the  patient.  Bulimia 
is  thus  one  of  the  characteristic  signs  of  acromegaly. 

SUBJECTIVE  SYMPTOMS    (ACCESSORY). 

Hearing,  Smell,  and  Taste.— "Th^  special  senses  are  not  generally 
disturbed,  but  in  exceptional  cases  affections  of  smell  and  hearing 
are  noted.  Hearing  may  be  disturbed  by  bone  growth  and  tinnitus 
aurium  may  be  a  very  troublesome  symptom.  (Cases  of  Osborne, 
Barclay-Symmes,  and  Holsti.) 

Cardiac  Palpitation.— Th:\s  has  been  referred  to  under  the  head- 
ing of  the  organs  of  circulation.  It  is  present  occasionally,  especially 
in  cases  where  enlargement  of  the  thyroid  or  thymus  is  found,  or 
where  the  great  increase  of  bodily  weight,  in  conjunction  with 
muscular  fatigue,  overtaxes  the  heart. 

GENERAIv   PSYCHIC   SYMPTOMS. 

Depression.— A.S  mentioned  at  the  beginning,  the  extraordinary 
changes  that  occur  in  the  physiognomy  and  in  the  hands  and  feet 
are  a  source  of  great  mortification  and  mental  distress  to  the  unfor- 
tunate subjects.  The  mind  is  naturally  affected,  and  depression  of 
the  spirits  is  the  natural  outcome  of  the  progress  of  this  grotesque 


28  ACROMEGALY 

disease.  The  temper  may  be  irritable,  and  impulses  of  a  suicidal  or 
homicidal  nature  are  recorded  (Osborne,  Pick,  Haskovec).  The 
memory  is,  as  a  rule,  unaffected.  In  cases  in  which  the  headaches 
are  violent  and  of  long  duration,  and  in  which  muscular  feebleness, 
lassitude  and  inability  to  pursue  the  usual  avocations  mark  the 
advance  of  the  disease,  it  is  but  natural  that  profound  mental 
depression  should  ensue.  In  the  latest  stage  coma  ushers  in  the 
fatal  termination. 

The  Nervous  System. — In  a  few  cases  we  have  organic  changes 
which  may  be  more  or  less  connected  with  the  disturbances  of 
the  pituitary  gland.  Epilepsy  is  one  of  these  and  has  been 
observed  by  Marinesco.  Drs.  Raymond  and  Souques  have  reported 
a  case  of  acromegaly  of  many  years'  standing  in  a  man  aged  54, 
who  in  the  last  three  years  had  developed  Jacksonian  epilepsy  lim- 
ited to  the  right  upper  extremity  and  right  side  of  the  face.  They 
stated  that  the  pituitary  gland,  in  their  opinion,  constituted  a  cere- 
bral tumor  capable  of  exciting  from  a  distance  the  cortical  psycho- 
motor centers. 

Marinesco's  case  was  that  of  a  woman  aged  32,  who  had  had 
epilepsy  at  22,  the  attacks  occurring  three  or  four  times  a  week. 
At  the  age  of  25  she  had  an  attack  of  giddiness,  in  which  she  fell 
from  a  second  floor.  Six  months  later  she  noticed  that  her  feet 
were  enlarged,  and  later  her  hands,  face,  and  abdomen.  The 
menses  ceased.  Strabismus,  polyuria  and  weakness  supervened. 
Sensibility  was  preserved  in  all  forms  except  vision.  Examination 
revealed  bitemporal  hemianopsia.  The  urine  contained  forty-eight 
grammes  of  sugar  per  liter. 

Paraplegia  has  been  observed  in  acromegaly  and  was  due  to 
pressue  of  the  tumor  on  both  motor  tracts  in  the  crura  cerebri.  In 
Pershing's  case  there  was  also  a  loss  of  bladder  and  rectal  control. 
Syringomyelia  has  been  found  coincident  with  acromegaly  by 
Holschewnikoff,  Frederick  Peterson,  and  Bassi.  In  the  first  case, 
however,  it  should  be  noted  that  there  was  no  affection  of  the  thy- 
roid and  thymus  or  of  the  pituitary  bodj^;  although,  on  the  other 
hand,  the  hands  were  large  and  hypertrophied  and  the  skin  covering 
them  was  thickened  in  the  superficial  and  deeper  layers,  and  the 
bones  of  the  hands  showed  small  exostoses.  The  second  case  has 
not  yet  come  to  autopsy. 

Bassi 's  was  a  remarkable  case,  in  which  syringomyelia  and 
solitary  tubercle  in  the  cerebellum  were  associated  with  cephalic 
acromegaly.  It  is  greatly  to  M.  Bassi' s  credit  that  he  was  able  to 
diasrnosticate  all  three  of  these  affections  intra  vitam,  and  he  was 


ACROMEGALY  29 

fully  corroborated  at  the  autopsy.  It  would  appear  that  the  syr- 
ingomyelia antedated  the  acromegaly  and  cerebellar  tubercle. 

Glioma  of  the  brain  and  apoplexy  were  noted  by  Pel  in  a  case  of 
acromegaly. 

Tinnitus  may  be  caused  by  the  pressure  of  the  growth  upon  the 
carotid  arteries. 

Paresthesias  and  pains  in  the  extremities,  according  to  Maxi- 
milian Sternberg,  are  frequent  in  acromegaly.  On  this  account 
many  cases  have  been  treated  and  considered  as  cases  of  rheuma- 
tism. Pressure  on  the  brachial  plexus  and  the  trigeminus  due  to 
bone  changes  has  been  noted  (Ascher). 

Great  sensitiveness  to  cold  is  recorded  in  several  cases,  and,  on 
the  other  hand,  one  case,  that  of  Rolleston,  had  a  subjective  sense 
of  heat  even  in  the  coldest  weather  and  felt  obliged  to  wear  thin 
clothing.  The  pains  are  consequent  on  the  extraordinary  tissue 
changes  and  are  sometimes  described  as  giving  the  sensation  of  the 
bones  being  torn  apart. 

The  symptom-complex  which  we  designate  as  acromegaly  may 
be  tabulated  in  the  following  manner,  as  M.  Sternberg  has  done,  or 
in  the  synoptical  chart  which  has  been  used  in  our  analysis  of  the 
cases  comprised  in  the  appendix  (not  included  in  the  present  pub- 
lication) : 

1.  Objective  symptoms:  {a)  Constant. — Enlarged  hands  and  feet; 
lengthening  of  face;  enlarged  eyelids;  excessive  enlargement  of  nose; 
prominence  of  cheek  bones;  enlarged  lips;  enlarged  chin;  prominent 
jaw;  kyphosis;  thickening  of  bones  of  thorax;  abdominal  respiration. 
((^)  Inconstant. — Prominence  of  supraorbital  arch;  exophthalmus; 
optic  nerve  atrophy;  hemianopsia;  impaired  hearing;  anosmia;  dis- 
ordered taste;  enlarged  larynx;  depth  and  roughness  of  voice;  Erb's 
dulness;  atrophy  of  testicles;  enlargement  of  penis;  enlargement  of 
abdomen;  atrophy  of  muscles;  reflexes;  enlargement  of  heart; 
increased  rate  of  pulse;  varicose  veins;  enlarged  lymphatic  glands; 
impotence;  sweats;  polyuria;  glycosuria;  disordered  sensibility;  pig- 
mentation; warts  and  moles. 

2.  Subjective  signs:  (a)  Constant. — Eoss  of  sexual  instinct; 
polyphagia;  polydipsia.  ((^)  Inconstant. — Headaches;  palpitation; 
dyspnea;  paresthesia;  vasomotor  neuroses. 

3.  General  and  psychic  symptoms:  General  weakness  and  ennui; 
melancholia. 

Varieties  of  Acromegaly. — Three  distinct  varieties  or  forms  of 
acromegaly  have  been  differentiated  by  M.  Sternberg.  They  are  as 
follows: 


30  ACROMEGALY 

1.  A  benign  form.     Duration,  about  fifty  years;  changes,  slight. 

2.  The  usual  chronic  form.     Duration,  eight  to  thirty  years. 

3.  An  acute  malignant  form.  Duration,  three  to  four  years.  In 
this  form  the  pituitary  is  sarcomatous. 

COURSE — DURATION. 

The  course  of  acromegaly  is  essentially  slow.  In  its  onset  it  is 
insidious,  and  for  that  reason  it  is  always  difficult  or  impossible  to 
fix  the  exact  date  of  its  inception.  In  the  case  of  women  we  may 
be  guided  somewhat  by  the  time  at  which  menstruation  ceased, 
and  in  this  sex  any  change  that  may  occur  in  the  size  of  the  hands 
and  feet  will  be  more  readily  noted  and  remembered.  There  is  diffi- 
culty, also,  in  making  any  positive  statements  as  to  the  arrest  of  the 
disease,  should  this  occur.  It  is  found  that  five  or  ten  years  or 
€ven  longer  may  elapse  before  menstruation  is  disturbed. 

There  is  some  variation  as  to  the  member  which  is  first  affected. 
Although  the  hands  are  probably  the  first  to  be  affected,  in  one  case 
(Kanthack's)  the  starting-point  was  the  left  foot,  and  the  second 
toe  grew  to  an  enormous  size.  In  Tamburini's  case  the  disease 
started  in  the  feet,  involving  next  the  head  and  then  the  upper 
-extremities.  The  occurrence  of  prognathism,  while  common  in 
acromegaly,  is  not  always  noticed  by  the  patients. 

Figs.  18  and  19  show  the  general  progress  of  the  disease.  The 
£rst  photograph  was  taken  eight  years  before  the  disease  first 
appeared;  the  second  was  taken  about  fifteen  years  after  its  origin, 
but,  as  we  have  intimated,  its  onset  was  so  gradual  and  insidious 
that  neither  she  nor  her  relatives  can  state  accurately  just  when  the 
trouble  began. 

Although  the  progressive  nature  of  the  disease  must  be  recog- 
nized, it  is  quite  likely  that  arrest  will  be  more  frequently  recorded 
as  its  nature  and  treatment  are  better  understood.  The  case  of 
Costanzo  and  a  recently  published  case  by  Vinke  are  probably  as 
encouraging  as  any  that  have  been  presented.  The  latter  patient 
was  treated  with  thyroid  and  pituitary  extracts,  alone  and  combined 
-with  each  other,  and  remained  under  treatment  for  five  months. 
The  results  in  both  instances  are  recorded  in  the  chapter  on 
Treatment. 

It  would  thus  appear  that  appropriate  treatment  may  be  followed 
"by  an  actual  diminution  in  the  size  of  the  hypertrophied  limbs. 

Two  stages  in  the  course  of  acromegaly  have  been  differentiated, 
-viz.,  the  erethic  stage  and  the  cachectic  stage  (Gauthier). 


ACROMEGALY  31 

The  phenomena  of  erethism  which  characterizes  the  first  stage 
embraces,  first,  a  painful  hyperesthesia  which  manifests  itself  in 
headaches  and  rheumatic  pains;  second,  a  hypertrophy  of  the  mus- 
cular fibers  which  may  give  to  patients  a  muscular  power  greater 
than  usual;  third,  palpitation  of  the  heart  accompanying  the  hyper- 
trophy of  that  organ;  and  finally  the  polyphagia  and  polyuria 
which  may  be  considered  to  be  connected  with  an  crethic  state  of 
the  respective  organs. 

The  second  stage  is  characterized  by  a  cachexia  or  a  period  of 
decadence.  The  stage  of  increase  has  abated  and  the  phenomena  of 
erethism  have  disappeared.  Muscular  atrophy  and  cardiac  dilata- 
tion and  a  consequent  enfeeblement  of  the  circulation  render  the 
patient  quite  helpless.  It  is  in  this  stage  that  bleeding  from  the 
nose  may  ensue,  and  progressive  debility  marks  the  period  of 
decline,  which  ends  in  syncope.     Epistaxis  may  also  occur  early. 

Tamburini  has  designated  the  stage  in  which  the  visual  functions 
are  interfered  with  and  in  which  headaches  develop  as  "  /«  phase 
hypophysaire. ' ' 

The  duration  of  acromegaly  may  cover  as  much  as  ten,  twenty 
or  thirty  years.  When  death  occurs  it  is  usually  by  syncope  ter- 
minating a  progressive  cachexia.  Death  has  occurred,  however, 
during  an  epileptic  convulsion. 

ANATOMY. 

The  discovery  of  acromegaly  has  awakened  great  interest  in  the 
anatomy  and  physiology  of  the  pituitary  body.  Indeed,  it  was  not 
until  1890  that  the  announcement  was  made  that  the  pituitary  body 
is  the  seat  of  such  marked  alteration  as  to  suggest  that  it  is  the/ons 
et  origo  mali.  To  Souza-L^eite  belongs  the  credit  of  this  observation. 
Up  to  that  point,  the  pituitary  body,  or  hypophysis  cerebri,  as  it  is 
termed,  was  regarded  with  indifference.  Descartes  had  made  its 
neighbor,  the  pineal  gland,  world-famous,  as  the  supposed  anatom- 
ical seat  of  the  soul;  but  the  pituitary  body,  as  that  name  implies, 
was  relegated,  in  the  minds  of  anatomists,  to  the  humble  duty  of 
secreting  the  nasal  mucus.  It  remained  contented  with  this  igno- 
minious office  until  its  emancipation  in  the  early  part  of  the  present 
decade,  and  during  these  latter  years  it  has  attracted  universal 
attention  and  assumed  gigantic  functions. 

The  pituitary  body,  hypophysis  cerebri  (German,  Hirnanhang), 
is  a  reddish  -  gray,  extremely  vascular  mass,  situated  in  the  sella 
turcica.     It  is  oval  in  shape  and  weighs  from  five  to  ten  grains. 


32  ACROMEGALY 

Boyce  has  made  a  careful  study  of  the  gland,  based  on  an 
examination  of  one  hundred  brains  of  insane  subjects,  dying  of 
intercurrent  affections.  The  weight  averages  .5  gramme,  ranging 
usually  from  .3  to  .6  gramme,  the  size,  apparently,  bearing  no 
relation  to  age,  and  more  particularly  to  sex  or  general  nutrition, 
or  to  the  size  of  the  brain. 

The  hypophysis  is  held  in  place  by  a  process  of  the  dura  derived 
from  the  inner  wall  of  the  cavernous  sinus.  There  is  a  small  hole 
in  the  center  for  the  passage  of  the  infundibulum.  ^ 

The  two  lobes  are  separated  from  each  other  by  a  fibrous  lamina. 
The  anterior  is  somewhat  the  larger,  oblong,  with  a  concavity 
behind,  in  which  the  round  posterior  lobe  is  received. 

The  anterior  lobe,  of  a  dark  yellowish-gray  color,  is  developed 
from  the  ectoderm  of  the  buccal,  or  primary  oral,  cavity,  and  resem- 
bles somewhat,  in  microscopic  structure,  the  thyroid  body.  It  con- 
sists of  isolated  vesicles  and  slightly  convoluted  tubular  alveoli  lined 
by  columnar  or  ciliated  epithelium  and  united  by  loose  vascular 
connective  tissue. 

A  majority  of  the  acini  are  solid;  they  occasionally  contain  a 
colloid  material,  similar  to  that  found  in  the  tubules  of  the  thyroid 
body.  Their  walls  are  surrounded  by  a  close  network  of  lymphatics 
and  capillary  blood-vessels.  Only  a  few  of  the  acini  at  the  edge  of 
the  smaller  lobe  are  hollow.  This  portion  of  the  gland  is  related 
to  the  alimentary  tract,  and  it  is  the  part  that  is  especially  liable  to 
disease. 

The  posterior  and  smaller  lobe  is  developed  by  an  outgrowth 
from  the  embryonic  brain  and  during  fetal  life  contains  a  cavity 
which  communicates,  through  the  infundibulum,  with  the  cavity  of 
the  third  ventricle.  In  the  adult  it  becomes  firmer  and  more  solid, 
and  consists  of  sponge-like  connective  tissue  arranged  in  the  form 
of  reticulating  bundles  between  which  are  branched  cells,  closely 
resembling  bipolar  or  multipolar  ganglion  cells.  This  portion  is 
evidently  vestigial  or  rudimentary  in  man. 

In  the  lower  animals  the  two  lobes  are  quite  distinct,  and  it  is 
only  in  the  mammalia  that  they  become  connected.  The  hypophysis 
thus  assumes  a  much  more  prominent  feature  in  the  brains  of  the 
lower  animals  than  in  the  case  of  man.  It  is  not  strictly  a  ductless 
gland,  but  its  secretion  is  poured  through  an  imperfect  system  of 
ducts  opening  between  the  dura  and  pia  mater. 

The  accompanying  illustrations  show  the  position  and  compara- 
tive size  of  the  embryonic  hypophysis  in  the  sheep  and  the  chicken. 

1  For  the  anatomical  description,  see  Gray's  Anatomy  and  a  description  by  Philip  Stohr. 


ACROMEGALY  33 

e;mbryoi.ogy. 

The  pituitary  and  thyroid  bodies  start  as  pouches  from  the  wall 
of  the  oral  cavity — but  growing  dorsad,  the  hypophysis  is  embraced 
between  the  ossifying  centers  at  the  base  of  the  skull  and  is 
thus  included  within  the  cranial  cavity.  Andriezen  states  that  it 
originally  "poured  its  secretion  into  the  current  of  a  water- vascular 
system  which,  beginning  at  the  mouth,  irrigated  the  cerebral  ven- 
tricles and  central  spinal  canal  of  the  earliest  vertebrates.  The 
main  function  of  this  system  must  have  been  respiratory,  but  the 
pituitary  gland  probably  furnished  some  substance  necessary  for 
the  proper  nutrition  of  the  nerve  tissue,  which  it  now  nourishes  less 
directly  through  the  blood  and  lymph"  (Pershing). 

Andriezen,  after  tracing  the  development  of  the  pituitary  body 
in  the  lower  vertebrates  through  the  amphibia  to  mammals  and 
man,  shows  that  its  related  size  does  not  keep  pace  with  the 
increased  growth  of  the  nervous  system,  an  indication  probably 
that  having  attained  the  acme  of  its  activity  in  lower  vertebrates,  it 
is,  in  higher  forms,  already  beginning  to  show  signs  of  diminishing 
activity,  though,  of  course,  still  functionally  active  even  in  man.^ 

There  is,  as  Andriezen  states,  an  obvious  parallelism  between 
the  thyroid  and  the  pituitary,  not  only  in  their  early  evolution  in 
vertebrate  animals,  but  also  a  physiological  relationship.  Thus 
we  can  explain  the  enlargement  of  the  pituitary  which  has  been 
observed  by  Stieda,  Rogowitsch,  Hofmeister,  and  Gley,  after  thy- 
roidectomy. But  Andriezen  notes  that  it  must  be  remembered, 
however,  that  ' '  the  pituitary  belongs  both  anatomically  and  physio- 
logically to  the  central  nervous  system,  while  the  thyroid  belongs  to 
the  respiratory  function  of  the  blood-vascular  system  and  thereby 
to  the  tissues  generally." 

All  of  these  investigations  point  to  the  important  trophic  influ- 
ence of  the  pituitar}^  gland  on  the  central  nervous  system.  Just 
how  this  operates,  we  are  as  yet  unable  to  state;  even  the  observa- 
tions on  the  experimental  destruction  of  the  pituitary  by  Horsley  in 
1886,  and  by  Gley,  Marinesco  and  others  in  1892-93,  appear  nega- 
tive; but  such  experiments  are  liable  to  defects  which  do  not  permit 
too  positive  conclusions.  Granted  that  Andriezen  is  correct  in  his 
own  conclusions  that  the  pituitary  gland  exercises  a  trophic  action 

1  Rogowitsch  has  found  that  after  thyroidectomy  in  dogs,  the  pituitarj'  gland  becomes 
swollen,  the  cells  vacuolated  and  ultimately  disintegrated.  Bourneville  and  Brecon  state 
that  in  sporadic  cretinism,  where  the  thyroid  gland  is  lost,  the  pituitary  body  has  been 
found  to  be  enlarged. 

Boyce  and  Beadles  found,  in  a  case  of  myxedema,  that  the  acini  and  extra-acinar  tissues 
were  filled  with  colloid-like  material  cells  and  that  the  cells  were  increased  in  size.  Abram 
found  changes  in  the  pituitary  in  a  case  of  carcinoma  of  the  thyroid. 


34 


ACROMEGALY 


Sheep 


StriaiujTi 


thse. 


Sup.  rrjxx 


Inf-, 


cochltcu 


Sheep 

Fig.  20.— (After  Dr.  Alec  Fraser, 


qcLTiqliXt> 


ACROMEGALY  35 

on  the  nerve  tissues,  enabling  them  to  take  up  and  assimilate  oxygen 
from  the  blood -stream  and  to  destroy  and  render  innocuous  the 
waste  products  of  the  metabolism,  and  these  two  functions  are 
intimately  related — in  fact,  really  one  process — so  that  an  adequate 
assimilation  of  oxygen  by  the  nerve  tissues  secures  an  adequate 
destruction  (by  oxidation)  of  the  waste  products. 

Thus  we  ma}^  expect,  a  priori,  that  the  results  which  would 
follow  removal  or  destruction  of  the  pituitary  body  would  be  those 
due  first  to  a  malassimilation  of  oxygen  by  the  nerve  tissues,  and 
simultaneously,  in  the  second  place,  to  an  insufficient  destruction 
and  consequent  accumulation  of  waste  products.  In  this  way  there 
ensues  a  rapid  nutritional  failure  and  death  of  the  central  nervous 
system.     The  results  would,  therefore,  be: 

1.  Depression  and  apathy  (the  commencing  failure  of  activity  in 
the  nerve  centers). 

2.  Muscular  weakness,  the  first  peripheral  effect. 

3.  lyoss  of  fine  coordination  and  equilibrium. 

4.  The  development  of  twitchings  and  irregular  contractions  or 
spasms  of  the  muscles. 

5.  Deficient  heat  production  and  subnormal  temperature. 

6.  A  wasting  of  the  body  tissues,  in  relation  to  the  more  rapid 
failure  of  the  central  nervous  system. 

7.  A  probable  compensatory  polypnea  or  dyspnea,  the  peripheral 
indication  of  the  failure  of  the  nerve  centers  to  assimilate  oxygen. 

8.  A  rapid  progress  toward  death.  ^ 

PATHOLOGY. 

Although,  as  we  have  noted,  the  hypophysis  has  been  observed 
slightly  enlarged  in  myxedema  and  cretinism,  it  remains  true  that 
in  acromegaly  we  have  the  only  disease  in  which  the  pituitary 
attains  any  considerable  size.  Gauthier  remarks  that  the  hyp- 
ophysis is  a  veritable  anpov  and,  consequently,  especiallj'  liable  to 
hypertrophy,  just  as  in  the  case  of  other  terminal  points  in  the 
economy.  I,  however,  do  not  lay  much  stress  upon  such  a  con- 
struction of  the  anatomy  of  the  hypoph3'sis,  as  I  believe  whatever 
pathological  changes  it  undergoes  are  entirely  referable  to  cellular 
and  developmental  characteristics  and  have  no  relation  to  gross 
physical  form. 

We  have  to  deal  with  the  remarkable  fact  in  acromegaly  that 
the  pituitary  body  has  a  tendency  to  increase  pari  passu  with  the 

1  For  a  fuller  account  of  the  histology  of  the  pituitarj-  body,  reference  is  made  to  the 
works  of  Luschka,  Langen,  Flesch,  Dostoiewsky,  r,othringer,  Rogowitsch,  Andriezen  (1894), 
Berkley  (1894),  Schouemann,  Slieda,  W.  Krause  (1876),  W.  Muller  (1S71),  and  Haller  (1S96). 


36 


ACROMEGALY 


Fig.  21. 


-Base  of  the  skull  of  the  American  giant,  showing  enlarged  pituitary  fossa,  com- 
pared with  normal  skull  from  the  collection  of  Dr.  George  McClellan. 


development  of  the  affection.  The  expansile  power,  coincident  with 
hypertrophy,  is  able  to  deform  and  hollow  out  the  bone  by  reason 
of  its  great  vascularity  and  proliferative  power.  The  sella  turcica  is 
dilated  into  a  cavity  of  corresponding  size.  In  an  extreme  case  the 
growth  presses  on  the  optic  commissure,  the  cavernous  sinus,  and 
on  the  carotid  artery;  on  the  third  and  fourth  nerves;  slightly  on 
the  ophthalmic  division  of  the  fifth  nerve;  on  the  uncinate  convolu- 
tion of  the  temporo-sphenoidal  lobe;  in  some  cases,  on  the  olfactory 
tract;  on  the  posterior  surface  of  the  orbital  convolutions;  on  the 
under  surface  of  the  crura;  on  a  part  of  the  internal  capsule  and 
thalamus,  and  even  on  the  anterior  surface  of  the  pons. 

In  Roxburgh's  and  Collis'  case  the  enlarged  pituitary  had  so 
pressed  upon  both  optic  tracts  and  the  chiasm  as  to  cause  a  total 
disappearance  of  the  left  tract  and  partial  destruction  of  the  right. 
The  dura  of  the  sella  turcica  presented  an  irregularly  eroded  and 
vascular  appearance,  and  the  irregularities  were  filled  with  an. 
extension  of  the  pituitary  growth. 


ACROMEGALY  37 

Enlargement  of  the  pituitary  fossa  is,  in  general,  a  fair  means  of 
determining  the  size  of  the  pituitary  body.  In  my  case  (the  giant) 
the  extreme  antero-posterior  diameter  is  2.7  centimeters  as  against  .8 
to  1.2  centimeters  in  the  normal  skull.  This  is  4.5  millimeters  larger 
than  Thomson's  and  Broca's  cases,  and  the  lateral  diameter  is  42 
millimeters  as  against  28  millimeters  in  the  normal.  In  Rothmell's 
case  the  pituitary  body  was  enlarged  to  the  size  of  a  hen's  egg  and 
weighed  476  grains  (32  grammes). 

We  cannot  overlook  the  fact,  however,  that  dilatation  of  the 
pituitary  fossa  by  itself  is  not  a  certain  proof  of  acromegaly. 

There  is,  in  the  Musee  Dupuytren,  a  skull  in  which  this  fossa 
measures  eighteen  millimeters  in  antero-posterior  diameter  in  which 
there  was  evidently  no  acromegaly,  as  the  face  is  normal  and  there  is 
no  hypertrophy  of  the  bones  of  the  skull.  The  specimen  originally 
showed  a  tumor  lying  between  the  brain  and  the  skull. 

Sarcoma  and  Other  Ttcmors  of  the  Pituitary  Gland. — In  one  of 
Mosse's  cases  the  hypophysis  was  found  to  be  replaced  by  a  "  fascic- 
ulated sarcoma"  weighing  36  grammes  (540  grains).  The  thyroid 
gland  had  undergone  cystic  degeneration;  the  thymus,  however, 
had  hypertrophied  and  assumed  a  pyramidal  form. 

In  Striimpell's  case,  reported  in  June,  1894,  and  which  had  been 
studied  for  a  long  time  in  the  clinic  at  Erlangen,  a  tumor  of  the 
hypophysis  was  found  having  the  character  of  a  malignant  sarcoma. 

In  Caton's  case  there  was  a  tumor  the  size  of  a  Tangierine 
orange,  occupying  a  much  dilated  sella  turcica  and,  apparently, 
sarcomatous. 

Adenoma  of  the  hypophysis  was  found  in  the  cases  of  Pearce 
Bailey,   Boltz,  Stroebe,  and  Tamburini. 

Boyce  and  Beadles,  Dallemagne,  Gauthier,  Marino,  and  Osborne 
found  cystic  degeneration.  In  the  description  of  Roxburgh's  and 
CoUis'  case  it  is  stated  that,  while  most  of  the  tumor  of  the  hyp- 
ophysis had  the  appearance  of  a  simple  hypertrophy,  the  peripheral 
and  especially  the  basal  portions  presented  characters  midway  be- 
tween those  of  a  glioma  and  a  round -cell  sarcoma. 

In  autopsies  in  acromegaly  the  hypophysis  has  always  been 
found  to  be  enlarged  or  diseased.  This  position  has  been  challenged 
on  insufficient  ground,  but  is  now  coming  to  be  accepted  as  correct.  ^ 
My  own  independent  study  and  conclusion  in  this  respect  is 
emphatically  corroborated  by  Maximilian  Sternberg,  who  has 
recently  made  the  unqualified  statement:  "Die  hypophysis  .  .  . 
ist  bei  Akromegalie  stets  erkrankt."     He  cities  forty-seven  autop- 

lAverage  weight  of  hypophysis  of  man  .5  to  .6  gramme. 


38 


ACROMEGALY 


sies  in  proof.  The  list  which  we  present  numbers  fifty  -  seven 
autopsies,  the  largest  number  hitherto  placed  on  record.  ^  They 
are  as  follows: 

Bailey,  2.2  x  1.6.  Henrot,  3x42  cm. 

De  Berg.  Holsti,  2.5  x  3  cm. 

Boltz  (i).  Lancereaux. 

(2).  Langer-Sternberg. 

Bonardi.  Linsmayer. 

Bourneville  and  Regnault  (Case  I).  Marie  and  Marinesco. 

Boyce  and  Beadles.  Mosse  and  Daunic,  weight  3.6. 

Brigidi,  2.8  X  3.8  cm.  Osborne. 

Broca.  Packard,  2.5  x  3  cm. 

Brooks'  and  Baruch's,  1.5  x  7  cm.  Pechadre  and  I,athuraz. 

Bury.  Pineles. 

Caton  and  Paul,  size  of  Tangierine  orange.  Rolleston,  size  of  walnut. 

Cepeda.  Rothmell,  weight  32,  size  hen's  egg. 

Claus.  Roxburgh  and  CoUis,  size  of  walnut. 

Comini.  Schultze,  4x2  cm. 

Dallemagne  (i),  size  of  pigeon's  &%%.  Sigurini  and  Caporiacco,  11x7x6. 

(2).  Smyth,  E.  J.,  5  X  7-5. 

(3),  size  of  nut.  Squance. 

Dalton.  Stroebe,  2.5  x     ,  size  of  nut. 

Dana,  3x3  cm.,  weight  2.  Striimpell,  2  x  2.5  cm. 

Duchesneau.  Tamburini,  5.3  x  3.9,  weight  2. 

Fraentzel.  Tikhomiroff. 

Fratnich,  5  x    .  Thomson,  size  of  walnut. 

Fritsche  and  Klebs.  UhthoflF. 

Furnivall.  Verga. 

Gauthier.  Wolf,  K.  (i). 
Godlee,  size  of  cherry.  (2). 

Griffith.  Worcester,  weight  58,  length  4.6  cm. 
Hanseman. 

DIMENSION'S    OF    PITUITARY   FOSSA   IN    SKELETONS. 

Regnault 3-i  ^  3.6      .... 

American  Giant  (Author's  case) 2.7  x  4.2  x  1.2 

Irish  Giant 3-8  x        x  2.8 

Byrne,  R.  C.  S.  E 2.2 

Hutchinson,  W 3-i  ^  3-8      .... 


In  Duchesneau' s  case  the  hypophysis  contained  a  wine-colored 
fluid,  which  was  attributed  in  part  to  the  fact  that  thirty- six  hours 
had  elapsed  at  the  time  of  the  autopsy.  Claus  shows  that  in  his 
case  the  autopsy  was  performed  betw^een  two  and  three  hours  after 
death,  and  the  fluid  found  could  not  be  accounted  for  by  cadaveric 
liquefaction,  but  must  have  been  due  to  a  process  of  degeneration  of 
the  affected  gland. 

In  about  12  per  cent,  of  specimens  of  hypophysis  in  acromegaly 
the  disease  is  a  true  sarcoma. 

Tumors   of  the   Hypophysis    Without  Acromegaly. — Drs.   J.    M. 

1  We  intentionally  omit  the  cases  of  the  Hagner  brothers  and  that  described  by  Sarbo; 
also  the  case  of  Somers.  In  the  latter  case  no  examination  was  made  of  the  brain,  and 
therefore  it  is  not  properly  included  in  lists  of  autopsies  in  acromegaly. 


ACROMEGALY  39 


Fig.  22. — Sarcoma  of  pituitary  in  a  case  of  acromegaly  (Striimpell). 

Anders  and  Henry  W.  Cattell,  in  1891,  reported  to  the  Philadelphia 
Neurological  Society  a  hemorrhagic  tumor  of  the  pituitary  body 
and  infundibulum,  unattended  with  any  signs  of  acromegaly.  The 
symptoms  in  life  had  been  anemia,  dizziness,  facial  neuralgia,  inter- 
nal strabismus,  and  general  weakness  and  nephritis.  Death  followed 
convulsions. 

In  a  case  which  occurred  in  the  practise  of  Weir  Mitchell  a  large 
aneurism  of  an  anomalous  artery  crossing  the  sella  turcica  entirely 
obliterated  the  hypophysis,  but  no  symptoms  of  acromegaly  ensued. 
It  might  be  urged,  however,  that  in  cases  of  this  class  a  deficiency 
of  the  pituitary  for  a  longer  period  of  time  might  be  followed  by 
symptoms  which,  it  is  well  known,  require  considerable  periods  for 
their  development. 

Reports  by  Weir  Mitchell  and  other  observers  bear  out  the 
statement  that  we  may  have  tumors  of  the  hypophysis  without 
signs  of  acromegaly.  Pearce  Bailey  has  recently  reported  a  case  of 
parenchymatous  hypertrophy  of  the  pituitary  with  death  due  to 
hemorrhage  into  the  gland  structure.  There  had  been  headache, 
dimness  of  vision,  blindness,  and  paralysis,  but  not  acromegaly. 

I  have  recently  observed  a  fatal  case  of  pleuro  -  pneumonia  in 
which  the  autopsy  revealed  a  large  tumor  of  the  hypophysis,  appar- 
ently sarcomatous;  the  case  presented  no  symptom  whatever  of 
acromegaly,  either  clinically  or  pathologically.     It  occurred   in  a 


40  ACROMEGALY 

colored  man,  a  native  of  North  Carolina,  38  years  of  age.  After 
a  short  illness  he  died  of  double  pleural  effusion,  hypostatic  pneu- 
monia, and  pulmonary  edema.  The  heart  was  hypertrophied;  there 
was  pericardial  effusion,  together  with  interstitial  nephritis,  arterio- 
sclerosis, and  fatty  infiltration  of  the  liver.  The  pia  mater  showed 
no  lesions;  dura  and  calvarium  normal.  There  was  no  lesion  of  the 
convexity  of  the  brain.  Occupying  the  position  of  the  pituitary 
body  was  a  tumor  measuring  3.5  centimeters  laterally  and  three 
centimeters  antero-posteriorly.  It  had  the  firmness  of  brain  tissue 
and  fitted  the  enlarged  sella  turcica.  The  walls  of  the  sella  were 
not  eroded,  excepting  as  regards  the  anterior  clinoid  process  on  the 
left  side.  Microscopic  section  showed  the  growth  to  be  a  round-cell 
sarcoma. 

In  the  experiments  which  have  been  undertaken  to  see  whether 
acromegaly  will  follow  the  destruction  of  the  pituitary  body,  it  is 
obvious  that  laboratory  experiments  of  this  nature,  performed  on 
such  small  animals  as  puppies  and  kittens,  for  example,  are  beset 
with  great  difficulties  in  execution;  and  it  would  be  natural  to  sup- 
pose, as  Pershing  has  remarked,  that  just  as  a  minute  remnant  of 
the  thyroid  left  in  an  operation  will  prevent  the  development  of 
myxedema,  so  a  proportionate  amount  of  the  pituitary  might  escape 
detection  and,  remaining,  defeat  the  purpose  of  the  experiment. 

Normal  Pituitary  in  Alleged  Acromegaly. — An  analysis  of  the 
cases  in  which  it  has  been  averred  that  autopsies  do  not  always 
reveal  changes  in  the  hypophysis  tends  rather  to  the  casting  of  doubt 
on  the  diagnosis  of  acromegaly  in  such  instances.  Such  cases  must 
be  very  few.  In  Sarbo's  case  the  patient  was  both  tuberculous  and 
syphilitic,  and  the  jaw,  nose  and  lips  do  not  appear  to  have  been 
enlarged.     The  skull  was  that  of  a  case  of  true  osteitis. 

The  cases  of  the  Hagner  brothers,  described  by  Friedreich  and 
Arnold,  are  doubtful  cases  also.  The  jaw,  nose,  lips  and  tongue 
were  not  enlarged.  The}^  had  extensive  and  general  enlargement 
of  every  bone  in  the  body,  due  to  osteitis.  Marie  regarded  them 
as  cases  of  hypertrophic  pulmonary  osteo-arthropathy. 

In  Bonardi's  case  the  pituitary  is  reported  normal. 

Absence  of  the  Pituitary  Gland. — Boyce,  in  an  autopsy  on  a  case 
of  phthisis,  discovered  that  the  pituitary  gland  was  absent. 

Thyroid  Gland. — This  has  been  considered  previously  (see  page 

13). 

Thymus  Glajid. — This  has  also  been  considered  previously  (see 

page  15). 


ACROMEGALY 


41 


Fig.  23. — Normal  and  acromegalic  skeletons  (Osborne). 


42  ACROMEGALY 

Changes  in  the  Spinal  Cord  and  Brain. — Arnold  found  the  periph- 
eral nerves  and  the  lower  part  of  the  cord  thickened,  with  increase 
of  the  interstitial  connective  tissue,  with  hyaline  degeneration  of 
the  nervous  elements.  There  was  degeneration  of  the  pyramidal 
tracts,  and  areas  of  cerebral  softening. 

Waldo  has  reported  a  case  where  an  oval  cavity,  one  centimeter 
in  diameter,  was  found  at  the  posterior  extremity  of  the  right 
hemisphere,  and  a  second  smaller  cavity  at  the  posterior  part  of  the 
second  temporo-sphenoidal  convolution;  also  two  others  at  the  ante- 
rior portions  of  each  of  the  lobes  of  the  cerebellum.  They  were 
probably  recent  and  due  to  emboli. 

I  have  already  referred  to  the  coexistence  of  acromegaly  and 
syringomyelia  (see  page  28). 

Bone  Struchire. — The  bone  shows  an  undeniable  dilatation  of 
the  vascular  orifices  and  an  enlargement  of  the  grooves  for  the 
course  of  vessels  along  the  bones  (Marie,  Broca).  Klebs  has 
noticed,  in  many  portions  of  the  affected  extremities,  the  larger 
size  of  the  arteries  and  capillaries  of  the  skin,  gaping,  on  section, 
and  infiltrated  and  surrounded  with  young  neoplastic  tissue.  This 
leaves  conspicuous  vascular  canals  and  osteophytic  growths  in  many 
of  the  skeletons,  so  that,  judging  from  these  preparations  in  muse- 
ums, we  notice  strong  resemblances  to  the  changes  in  osteo-arthritis 
and,  in  a  lesser  degree,  the  appearances  in  osteitis  deformans.  We 
are  in  need  of  a  good  account  of  the  minute  bone  changes  in 
acromegaly. 

Other  Z"mz^<?5.— Marinesco  found  that  in  the  great  toe  all  the 
structures  were  hypertrophied,  even  the  membrana  propria  of  the 
sweat  and  sebaceous  glands,  and  that  the  external  coat  of  the  blood- 
vessels had  undergone  a  notable  hj'pertrophy.  But  most  marked  of 
all  was  the  increased  thickness  of  the  sheaths  of  the  subcutaneous 
nerves.  The  nerves  themselves  were  degenerated;  the  alterations 
in  larger  nerves  were  much  slighter.  In  the  bones  there  was  a  new 
formation  of  bony  tissue  and  an  increase  in  both  the  length  and 
thickness  of  the  bones.  The  enlargement  of  the  tongue  was  found 
to  be  due  to  increase  in  the  connective  tissue  and  the  size  of  the 
bundles.  The  cervical  sympathetic  was  found  sclerosed,  especiall}^ 
the  lowest  ganglion.  The  kidneys  showed  a  condition  of  cortical 
nephritis.  The  follicles  of  the  atrophied  thyroid  were  enlarged 
and  cystic,  the  nasal  mucous  membrance  was  thickened  and  mam- 
millated,  and  the  vessels  w^ere  sclerosed  and,  in  parts,  almost 
obliterated. 


ACROMEGALY  45 


^i^^H^il^HHHii^Hli^H^   57- 
IHI^^^Hi^H^BI^^i^HI^Hi  57- 

I^^I^B  Thyroid  examined,  36. 

Thyroid  hypertrophied,  13. 

Thyroid  atrophied,  11. 

Thyroid  normal,  12. 

Thymus  examined,  26. 

Thymus  hypertrophied  or  present,  12. 

Thymus  absent,  13. 

Sympathetic  ganglia  examined,  11. 

^^^HB  Sympathetic  ganglia  diseased,    7. 

Fig.  24— Autopsies  in  57  undoubted  cases  of  acromegaly.  Three  doubtful  cases  are  not 
included  herewith.  In  each  of  the  57  cases  the  hypophysis  was  examined  and  found  to- 
be  diseased. 

ETIOLOGY. 

During  the  years  that  have  elapsed  since  the  discovery  of  this 
remarkable  disease,  no  great  advances  have  been  made  as  regards 
the  true  explanation  of  its  causation.  The  various  theories  that 
have  been  enumerated  will  be  duly  considered  hereafter. 

Heredity .—Vi  has  been  denied  that  heredity  has  any  influence  in 
the  causation  of  acromegaly.  There  is,  however,  some  evidence  to- 
show  that  it  has  been  observed  as  a  congenital  affection. 

Cenas  has  described  the  case  of  a  boy  aged  15  years  which  he 
believes  to  be  congenital  acromegaly.  At  birth  there  was  asym- 
metry of  the  face  and,  after  a  few  months,  the  child  exhibited 
deformities  of  the  hands.  At  four  years  there  were  pigmented  spots- 
on  the  hands  and  feet;  these  members  had  increased  steadily  in  size 
at  seven  years,  but  there  was  only  slight  change  in  his  arms  and 
legs;  they  were  clumsy.  The  head  was  enlarged  and  the  hands 
were  covered  with  violet  discolorations.  The  feet  were  enormous. 
There  was  asymmetry  of  the  tongue,  cheek,  and  lips.  The  lower 
jaw  was  hypertrophied  and  there  was  kyphosis. 

The  famous  cases  of  the  Hagner  brothers  which  have  been, 
studied  by  Erb  and  Arnold  have  been  cited  to  support  the  view  that 
a  family  type  may  exist.  Marie,  however,  denied  this,  as  regards 
these  cases;  but  Jonathan  Hutchinson  gave  his  opinion  regarding 
them  as  follows:  "If  I  may  venture  a  suggestion  in  a  question  so- 
full  of  intricacy,  it  would  be  that  they  are,  after  all,  examples  of 
what  may  be  called  the  family  form  of  acromegaly." 

It  was  Arnold  who  made  the  autopsy  in  one  of  these  cases,  and 


44  ACROMEGALY 

he  gave  to  the  affection,  as  he  observed  it  in  these  subjects,  the 
name  of  "  pachyacria." 

In  Field's  case,  reported  as  acromegaly,  although  of  doubtful 
type,  the  symptoms  were  present  and  the  case  published  when  the 
child  was  seventeen  months  old. 

Moncorvo  reported,  in  1892,  a  case  of  what  seems  to  be  con- 
genital acromegaly.  It  occurred  in  an  idiotic  child  of  fourteen 
months.  The  remarkable  feature  of  the  case  was  that  the  head  was 
microcephalic,  while  the  hands,  fingers  and  feet,  the  nose  and  lips, 
were  verj^  much  hypertrophied.  Yon  Recklinghausen  and  A'^er- 
straeten  believe  in  a  hereditar}^  influence  in  the  etiolog}"  of  the 
disease. 

Sex. — In  130  cases  in  the  appendix  we  find  that  seventj'-three 
were  males  and  fift^^-seven  females. 

Race. — One  case,  that  of  Berkley,  was  in  the  negro  race. 

Age. — The  j^oungest  case  reported  is  fourteen  months.  The 
oldest  patient,  at  the  time  of  report,  was  that  of  Gordinier,  aged  77. 

The  age  at  onset  of  the  disease  was  as  follows:  o-io  3'ears,  4 
cases;  11-20  years,  19  cases;  21-30  j^ears,  33  cases;  31-40  j^ears,  22 
cases;  41-50  years,  10  cases;  51-60  years,  2  cases;  61-70  years,  i 
case;  71  years,  i  case. 

Depressing  emotions  have  been  assigned  a  place  in  the  etiology 
of  the  disease.  I  believe,  however,  that  this  is  wholly  an  effect 
and  not  a  cause  of  the  disease.  Chills  have  been  mentioned  as  a 
cause,  but  I  see  no  reason  for  this. 

Traiuna. — This  has,  no  doubt,  some  influence  in  setting  in  oper- 
ation the  cerebral  changes  which  are  found  in  acromegal3\  I 
have  found  trauma  noted  in  the  history  of  19  out  of  130  cases. 
Marinesco's  case  is  a  striking  instance  in  point.  The  patient,  who 
was  25  5'ears  of  age  at  the  time  of  her  accident,  fell  from  the  second 
floor  of  a  building  and  received  an  injury  to  the  head  from  which 
she  was  unconscious  for  three  hours.  Epileps}^  supervened,  and 
also  the  usual  symptoms  of  acromegal3^  Baruch's  case  had  a  his- 
tor}^  of  having  fallen  twent}^  feet,  striking  upon  his  head.  This 
occurred  five  years  before  the  patient's  death  and  about  two  j^ears 
before  the  symptoms  of  acromegaly  were  observed. 

Gauthier's  patient  had  two  falls  in  which  his  head  forcibly 
struck  the  ground.  The  patient  attributed  his  disease  to  these 
accidents. 

In  Farge's  case  there  was  a  severe  accident,  disabling  the  patient 
for  ten  months,  and  it  was  during  this  time  that  the  first  sj'mptoms 
of  acromegaly  were  said  to  have  been  noticed. 


ACROMEGALY  45 

Other  cases  in  which  trauma  has  been  noted  are  those  of  Uuver- 
richt  Barclay,  Benson,  Marie,  Bourneville  and  Regnault,  Bramwell, 
Pel,  'Chauffard,  Gauthier,  I^avielle,  Ruder  and  Marmesco  (2), 
Brooks    Strzeminski,  Haskovec,  and  Remington. 

Rheumatism  is  also  said  to  be  a  cause.     We  have  seen,  however, 
that  in  the  erethic  stage  there  are  hyperesthesias  and  pams  about 
the  extremities  that  resemble  rheumatism  very  closely  and  that  have 
civen  rise  to  the  belief  that  many  of  these  patients  had  rheumatism 
Such  was  true  of  the  cases  of  Vinke   and    Cunningham,    and  of 

others.  .  , 

Arthritis    as  it  is  observed  in  the  early  stages  of  acromegaly 
{e.g.,   in    the   case   of    Middleton),   is   probably   a   purely   trophic 

change.  .  , 

Infective  Disease s.-'^\^^s^  do  not  play  a  very  conspicuous  part. 
Syphilis  is  not  a  factor  in  the  histories  of  these  cases;  neither  is- 
alcoholism,  variola,  scarlatina,  or  intermittent  fever-although,  natu- 
rally, the  patients  have  had  some  of  these  affections  at  some  time  m 
their  past  history. 

THEORIES  OF  THE  ETIOLOGY  OF  ACROMEGALY. 
A  review  of  the  various  theories  which  have  been  advanced  to. 
explain  the  occurrence  and  course  of  acromegaly  would  lead  us  into 
a  maze  of  discussion  from  which  we  naturally  shrink.  The  gen- 
eral drift  of  the  later  writers  leads  to  the  belief  that  we  are  dealing 
with  a  disease  of  a  trophic  nature,  depending  on  a  perversion  ot 
function  of  the  pituitary  gland;  these  changes  being  brought  about 
through  the  medium  of  an  "internal  secretion,  like  that  of  the 
thyroid,  which  acts  chiefly  upon  the  trophic  fibers  of  the  peripheral 

nervous  system." 

Although  I  shall  endeavor  to  give,  as  briefly  as  may  be, 
the  opinions  of  twelve  competent  men  in  the  premises,  it  will  be 
found  that  the  jury  will  fail  to  agree  upon  a  verdict;  for  each  one 
takes  a  distinctly  different  view  of  the  case,  as  it  has  been  presented 

for  his  judgment.  .  -rr-     • 

Marie's  own  view  is  entitled  to  the  first  consideration.  His  is- 
the  -theorie  hypophysaire,-  in  which  he  attributes  to  the  changes  m 
the  pituitary  body  all  the  phenomena  of  the  disease.  He  believes 
that  this  gland  possesses  a  function  analogous  to  that  performed  by 
the  thyroid  body  in  myxedema.  The  changes  throughout  the 
system  constitute  a  systematized  dystrophy,  depending  on  an  altera- 
tion of  the  hypophysis,  which  henceforth  becomes  incompetent  to 
neutralize  certain  toxic  substances  the  accumulation  of  which  m  the 


46  ACROMEGALY  ^ 

blood  brings  about  the  various  changes  of  acromegaly.     Marinesco 
supports  this  position. 

The  Theo7'y  of  Trophic  Neurosis.  —  In  this  theory,  not  yet 
demonstrable  by  any  anatomical  evidence  as  far  as  I  can  find,  the 
nervous  system  is  held  accountable,  primarily,  for  all  the  patho- 
logical phenomena.  The  changes  observed  in  the  pituitary  body 
are,  therefore,  considered  to  be  of  a  secondary-  nature,  this  structure 
sharing  with  other  organs  the  morbid  process. 

The  added  influence  of  the  diseased  pituitary,  which  we  have 
seen  to  be,  almost  without  exception,  disordered,  will  be  felt  in  the 
phenomena  of  autointoxication  and,  hand  in  hand  with  the  action  of 
the  diseased  thyroid  bod}^,  the  trophic  disturbances  are  augmented. 
This  is  the  theory  of  von  Recklinghausen  and  Holschewnikow,  and 
is  supported  by  Mosse  of  Toulouse.  Mosse  cites  in  its  support  the 
-early  occurrence  of  vasomotor  disturbances,  local  asph3'xia  of  the 
extremities. 

Thus  we  have,  first,  a  trophic  neurosis;  second,  toxic  phenomena, 
■due  to  disorder  or  suppression  of  the  internal  secretions  of  the 
pituitary  and  thyroid  glands.  The  author  believes  that  this  is  the 
more  rational  view^,  and  that  in  the  absence  of  anatomical  proof 
the  more  favorable  results  following  the  administration  of  thyroid 
extract,  either  with  or  without  the  use  of  the  pituitary  gland,  afford 
a  therapeutic  corroboration  of  this  line  of  argument.  The  use  of 
these  preparations  is  based  on  the  belief  that  they  supply  the  pro- 
tecting elements  which,  in  its  diseased  state,  the  system  lacks,  and 
that  they  are  able  to  check,  to  some  extent,  the  toxic  process.  This 
theory  is  in  harmony  with  that  of  Horsley,  who  seeks  in  a  similar 
w^aj^  to  establish  the  relation  of  the  thyroid  body  to  m5'xedema. 
That  the  pituitary  and  th5'roid  bodies  and  the  thymus  are  inter- 
related seems  highly  probable,  when  we  consider  the  striking  analo- 
gies between  the  d3^strophies  of  acromegaly,  myxedema,  and  cretin- 
ism, and  the  changes  in  all  three  of  these  glands  observed  in  the 
various  forms  of  acromegaly.  ^ 

It  may  be  that  in  case  of  impairment,  destruction  or  physiolog- 
ical quiescence  of  either  of  these  glands,  the  remaining  glands  may 
fulfil  its  function,  just  as,  after  removal  of  the  spleen,  life  is  pre- 
served by  compensatory  action  (see  Kron's  case). 

Claus'  investigations,  as  well  as  those  of  Rogowutsch,  Vassali, 
Sacchi  and  Hofmeister,  seem  to  show  that  ablation  of  the  thyroid 
was  followed  by  hypertrophy  of  the  hypophysis,  and  vice  versa. 

iSee  monograph  by  G.  Buschan  on  Myxedema  and  Allied  Conditions  and  the  Physiology 
.and  Therapeutic  Uses  of  the  Thyroid  Gland,  Leip.sic,  1896.  Extensive  bibliography;  182 
pages. 


ACROMEGALY  47 

According  to  Schaefer  and  Oliver,  they  are  physiologically 
antagonistic.  In  view  of  the  superficial  resemblance,  in  some 
respects,  between  acromegalj'  and  myxedema,  it  might  be  held  that 
"acromegaly  is  a  result  of  a  disturbance  of  a  chemico-phj'siological 
equilibrium,  maintained,  in  health,  by  the  normal  activity  of  these 
two  glands  .  .  .  and  thus  the  cause  of  the  disease  is  perverted, 
and  not  suppressed  or  exaggerated,  functional  activity  of  the  gland  " 
(Rolleston). 

Vassali  and  Sacchi,  by  their  investigations,  show  that  the  func- 
tion of  the  pituitary  is  essentially  trophic,  enabling  the  nerve  tissues 
to  take  up  and  assimilate  oxygen  from  the  blood-stream.  It  also 
exerts  an  influence  on  metabolism,  destroying  or  rendering  innocu- 
ous certain  waste  products. 

According  to  Tamburini,  there  are  two  distinct  phases.  In  the 
first,  there  is  hyperf unction  of  the  gland  and  hypertrophy;  in 
the  second,  there  would  be  an  adenomatous  change,  as  in  the  case 
of  Claus  and  Vanderstrict,  or  sarcomatous,  as  in  Dallemague's  first 
case,  or  cystic,  as  in  his  second  and  third  cases;  and  then,  clinically, 
^vould  follow  cachexia  and  death. 

Massolongo  supports  Tamburini  and  assigns  acromegaly  to  the 
class  of  autointoxications.  He  seems  to  have  antedated,  by  two 
years,  Tamburini's  views  as  to  the  hyperfunction  or  hyperactivity  of 
the  pituitary. 

Dallemagne  shows  that  we  have  not  yet  arrived  at  even  an 
-elementary  knowledge  of  the  laws  governing  the  equilibrium  of 
nutrition.  We  must  admit  the  fact  of  such  an  equilibrium;  the 
proportions  of  our  various  members,  the  dimensions  of  organs,  and 
our  entire  anatomical  type  are  governed  by  natural  laws,  the  opera- 
tion of  which  we  have  not  even  begun  to  understand. 

It  is  highly  probable  that  nutrition  or  trophic  centers  exist  at 
various  points  in  the  central  nervous  system.  Dallemagne  is 
inclined  to  connect  the  changes  which  the  pituitary  body  undergoes 
with  ''''proliferations  qui  encombrent  le  canal  central,'''  which  latter  is 
considered  as,  after  all,  simply  the  upper  cul-de-sac  of  this  canal. 

On  the  supposition  that  the  central  canal  is  emuuctory  in  its 
function,  its  epithelium  would  have  a  role  analogous  to  that  of 
the  renal  epithelium,  and  we  may  assign  at  various  points  in  the 
■cord  these  centers  of  equilibrium  of  nutrition,  to  create  a  sort  of 
nutritive  metamerism. 

Thus  it  would  follow  that  disturbances  of  these  centers  of  equi- 
librium would  be  followed  b}^  exaggeration  of  form,  due  to  the 
anomalous  state  of  nutrition,  and,   further,   abnormal  products  of 


48  ACROMEGALY 

this  diseased  nutrition  would  be  put  in  circulation.  In  this  manner 
irritative  troubles  of  a  secondarj^  nature  would  be  set  on  foot  and, 
perhaps,  particularly  about  the  ependymal  (central)  canal.  Thence 
would  arise  the  affections  assigned  to  this  canal,  and  especially  the 
modifications  of  the  hypophysis. 

Dallemagne  holds  that  the  changes  observed  in  the  hypophysis 
are  a  result  and  not  a  cause,  no  matter  how  the  cause  operates.  The 
origin  of  the  troubles  must  be  in  the  centers  which  preside  over 
equilibrium  of  nutrition,  on  which  the  proportion  of  our  various 
members  depends. 

As  regards  bone  formation,  the  views  of  Marinesco  are  of  interest 
in  this  connection.  He  holds  that  the  development  of  normal  bone 
is  dependent  upon  the  pituitary  and  thyroid  glands.  "  It  is  probable 
that  they  secrete  substances,  such  as  soluble  ferments,  necessary  for 
stimulating  and  carrying  on  the  normal  osteo-genetic  process."  We 
know,  moreover,  as  Hofmeister  has  shown,  that  there  exists  nor- 
mally in  thyroidectomized  animals  an  atrophy  of  the  osseous  tissue. 
Or  else,  in  acromegaly,  the  equilibrium  of  nutrition  of  bone  is 
disturbed  and  the  nerve  force  necessary  for  the  regulation  of  the 
osteo-genetic  process  is  destroyed;  then  is  produced  this  abnormal 
process  of  the  bones  of  the  extremities  and  of  the  bony  extremities. 

Other  theories  as  to  the  pathology  of  acromegaly  have  a  historic 
rather  than  a  practical  interest.  We  have  the  theory  of  Klebs.  He 
assigns  the  affection  to  an  exaggerated  development  of  the  vascular 
system,  in  which  the  thymus  gland  plays  an  important  part.  The 
affection  would  thus  be  a  thymic  angiomatosis,  in  which  occurs  a 
general  proliferation  of  vascular  germs  or  angioblasts.  Gauthier 
seems  to  believe  in  the  theory  of  angiomatosis. 

Freund  and  Verstraetem  refer  this  affection  to  a  pathologic  proc- 
ess, little  known  up  to  the  present,  but  seated  in  the  essential  organs 
of  reproduction.  They  discover  in  it  the  result  of  an  ''inversion 
dans  V evolution  de  la  vie  genitale.''  According  to  their  view,  acro- 
megaly belongs  to  a  fresh  pathologic  family,  originating  in  perver- 
sion of  the  genital  life  and  including  infantilism  and  gigantism.  The 
genital  function  is,  as  a  rule,  found  to  decline  at  an  early  age. 

This  theory  is  based,  to  begin  with,  on  the  alleged  appearance  of 
the  first  symptoms  about  the  age  of  puberty.  This  is  too  slender  a 
foundation,  in  my  observation.  It  is  also  based  on  the  usual  exist- 
ence and  early  appearance  of  genital  disturbances. 

Freund  is  credited  with  an  observation  to  this  effect:  that,  in  his 
studies  of  development,  as  seen  in  negroes  and  the  anthropoid  apes^ 
he  has  been  led  to  think  that  acromegaly  is  a  sign  of  atavism  ! 


ACROMEGALY  49 

Bacteriology  has  been  invoked  by  Arnold  to  yield  an  explana- 
tion, but  no  information  has  been  elicited  from  that  source. 

Without  lingering  further  over  the  various  speculations,  we  may 
group  the  views  of  investigators  with  reference  to  the  function  of 
the  pituitary  gland  and  its  relation  to  acromegaly  as  follows: 

That  the  essential  symptoms  are  due  to  an  alteration  of  the 
internal  secretion  of  the  gland.  Three  forms  of  modification  are 
suggested  (see  Rolleston): 

I.  Suppression,  a  condition  of  incompetency  of  the  pituitary 
gland,  analogous  to  myxedema  or  Addison's  disease.  Such  incom- 
petency would  imply  either  an  atrophy  of  the  pituitary  gland,  which 
is  not  in  accordance  with  the  post-mortem  findings,  the  reverse  being 
the  case;  or  else  destruction  by  a  tumor. 

It  has  been  suggested  that  the  simple  absence  of  the  internal 
secretion  cannot  be  the  entire  explanation,  because  cases  have  not 
improved  satisfactorily  by  treatment  by  pituitary  extract.  This 
argument,  however,  I  consider  to  be  open  to  criticism. 

II.  Hypersecretion,  due  to  excessive  activity.  This  view  is 
borne  out  by  observations  of  simple  hypertrophy  of  the  hypophysis. 
The  administration  of  pituitary  extract  would  be  expected  to  aggra- 
vate the  symptoms. 

III.  Perverted  function,  due  to  heterogeneous  transformation  of 
the  structure  of  the  pituitary  body.  Rolleston 's  statement  on  this 
head  is  clear,  and  we  will  give  it  as  he  makes  it — taking  it  from 
Marie  and   Marinesco: 

1.  The  secretion  might  be  deficient  in  an  active  principle,  the 
function  of  which  is  to  restrain  exuberant  growth  in  the  extremities. 
This,  perhaps,  is  rendered  improbable  by  the  general  failure  of  pitu- 
itary extract  when  given  medicinally,  and  there  is,  of  course,  no 
evidence  that  irregular  growth  is  spontaneously  likely  to  occur  if 
not  kept  in  check. 

2.  The  abnormal  secretion  might  contain  some  toxic  principle 
which  stimulated  the  tissues  to  overgrowth.  That  the  disease  is  a 
toxemia  receives  some  support  from  its  points  of  resemblance  to 
hypertrophic  pulmonary  osteo-arthropathy,  for  Marie  has  suggested 
that  the  changes  in  the  limbs  characterizing  the  latter  disease  were 
due  to  the  local  action  of  poisons  absorbed  from  the  pulmonarj' 
lesions. 

3.  It  might  be  thought  that,  owing  to  alteration  in  the  secretion 
of  the  pituitary,  the  equilibrium  and  interaction  between  it  and 
other  internal  secretions  are  disturbed.  Possibl}^  some  toxic  body, 
such  as  was  suggested  in  the  preceding  alternative,  might  be  thus 
produced. 


50  ACROMEGALY 

It  is  possible,  also,  to  suppose  that  there  is  some  primarj^  nervous 
lesion  of  unknown  character  and  that  the  glandular  changes  consti- 
tute a  series  of  phenomena  of  the  second  order.  Arnold,  Dercum 
and  Dreschfeld  have  suggested  such  a  view. 

Cases  occur  occasionally  which  seem  to  be  examples  of  general 
involvement  of  the  glands  of  internal  secretion,  the  inference  being, 
very  naturally,  that  these  glands  are  affected  by  a  cause  common  to 
them  all.  In  five  such  cases  collected  by  Murray  acromegaly  and 
exophthalmic  goitre  coexisted  in  each;  in  four  of  them  glycosuria 
was  present.  In  two  fatal  cases  the  thyroids  as  well  as  pituitaries 
were  enlarged,  and  one  of  them  showed  an  enlarged,  persistent 
thymus  gland.     Lancereaux  has  called  attention  to  similar  cases. 

ACROMEGALY   AND    GIGANTISM. 

When  it  became  known,  five  years  ago,  by  the  independent  obser- 
vation of  Tamburini,  Brissaud,  and  Taruffi,  that  the  pituitary-  body 
undergoes  a  remarkable  hj^pertrophy  in  the  case  of  a  large  per- 
centage of  giants  and  was  probabl}'  an  agent  of  great  importance  in 
producing  these  wonders  of  the  world,  the  hj'pophysis  maj-  be 
considered  to  have  reached  the  pinnacle  of  its  power.  In  the  giants 
that  came  to  post-mortem  examination,  the  pituitarj'  was  found 
truly  h3'pertrophied. 

In  the  skeletons  of  giants  that  were  forthwith  examined,  unmis- 
takable evidences  of  acromegaly  were  found.  The  skeleton  of  which 
I  furnish  the  measurements  shows  this  in  a  moderate  degree.  The 
pituitary  fossa  is  the  largest  on  record,  measuring  27  millimeters 
antero  -  posteriori}",  42  millimeters  laterallj',  and  12  millimeters  in 
depth.  Thus  we  find  that  the  celebrated  "Irish  giant,"  Cornelius 
McGrath,  described  b}-  Cunningham,  had  undoubted  evidences  of 
acromegaly,  including  a  huge  pituitary  fossa.  So,  also,  it  was 
found  bj'  Taruffi  that  the  giant's  skeleton  which  he  examined  in 
Reggio  was  also  that  of  an  acromegalic.  W.  Hutchinson,  who 
has  made  a  stud}'  of  this  subject,  estimates  that  from  40  to  60  per 
cent,  of  giants  are  also  cases  of  acromegaly.  He  cites  the  fact  that 
of  over  one  hundred  cases  on  record,  only  one  lived  to  old  age,  very- 
few  to  middle  life,  and  a  majority  died  before  the  age  of  thirty, 
many  deaths  being  due  to  a  general  failure  of  the  vital  powers,  or 
some  trivial  intercurrent  disease  imposed  upon  this. 

"  Myth  and  popular  impression  to  the  contrary  notwithstanding, 
giants  are  a  short-lived,  feeble-minded,  weak-bodied  race,  sham- 
bling in  their  movements,  and  of  the  mildest  dispositions.  They 
are  occasionally  possessed  of  great  power,  but  this  seldom  lasts  more 


ACROMEGALY  51 

than  a  few  years,  just  as  is  also  seen  in  some  cases  of  acromegaly. 
The  position  which  appears  to  us  best  to  harmonize  these  facts  is 
that  acromegaly  and  gigantism  are  similar,  if  not  identical,  disturb- 
ances of  pituitary  metabolism,  the  one  beginning  in  early  life,  before 
the  full  stature  has  been  reached,  and  producing  comparatively  sym- 
metrical results,  extending  over  a  considerable  period;  the  other 
developing  after  maturity  and  expending  its  overgrowth  force  at 
the  points  of  least  resistance  to  growth— the  hands  and  feet,  nose 
and  lower  jaw.  In  both,  the  essential  process  is  a  more  or  less 
rapid  overgrowth,  reaching  a  definite  limit,  and  soon  followed  by 
correspondingly  rapid  decay.  The  ultimate  result  is  the  same  in 
both:  the  situation  of  the  outgrowth  (extremities  and  distal  por- 
tions of  appendicular  skeleton  generally)  is  strikingly  similar;  there 
is  the  same  disturbance  of  the  sexual  functions — in  fact,  almost  the 
only  differences  between  them  are  in  the  pressure  symptoms  (head- 
ache, hemianopsia)  and  more  rapid  course  of  the  adult  form." 

Maximilian  Sternberg  distinguishes  two  forms  of  gigantism — 
first  the  normal,  and  second  the  pathological,  which  almost  always 
is  associated  with  acromegaly.  In  thirty -four  cases  of  gigantism 
examined,  he  finds  evidences  of  acromegaly  in  fourteen  (42  per 
cent.),  which  shows  that  gigantism  predisposes  to  acromegaly;  on 
the  other  hand,  acromegaly  predisposes  less  to  gigantism. 

It  is  in  this  second  class  that  we  find  prognathism  and  enlarge- 
ment of  the  sella  turcica.  Sternberg  exhibited  recently,  in  a  discus- 
sion of  this  subject,  a  typical  skull  from  both  varieties  of  gigantism. 
He  considers  gigantism  and  acromegaly  as  separate  entities  and 
states  that  only  about  20  per  cent,  of  acromegalics  are  above  1.80 
meters  (6  feet)  in  height,  and  that  above  40  per  cent,  of  giants  are 
acromegalic.  Gigantism,  therefore,  is  considered  by  him  as  predis- 
posing to  acromegaly;  one  of  their  tendencies  to  trophic  organic 
changes  being  acromegaly.  Nearly  half  the  giants  die  from  this 
cause.  Marie  puts  it  this  way:  "Acromegaly  is  gigantism  of  the 
adult;  gigantism  is  acromegaly  of  the  adolescent." 

As  to  the  two  types  of  acromegaly,  there  is  a  disposition  to 
assume  the  long  or  giant  type  of  acromegaly,  if  the  disease  origina- 
ted in  the  period  of  adolescence;  but  if  the  onset  is  delayed  until 
later  life,  the  type  will  be  large  (Brissaud  and  Meige). 

In  a  case  of  Dallemagne  acromegalic  symptoms  appeared 
fifteen  years  previous  to  observation,  and  for  many  years  before 
that  the  patient  had  gigantic  stature.  After  death  the  heart, 
kidneys,  liver  and  spleen  were  double  and  even  triple  the  normal 
weight.     This  author  considers  that  this  enormous  increase  should 


52  ACROMEGALY 

be  attributed  more  to  the  acromegaly  than  to  the  gigantism.  He 
terms  it  a  sort  of  splanchnomegaly,  referable  to  the  same  process  as 
obtains  in  hypertrophy  of  the  extremities. 

A  case  described  by  Brissaud  and  Meige  was  as  follows:  The 
man  presented  nothing  abnormal  before  the  age  of  i6;  he  then 
rapidly  grew  larger,  and  at  21  years  he  measured  7  feet  2  inches 
and  weighed  340  pounds.  He  remained  well  and  spry  until  the  age 
of  37,  when  his  spine  gave  way  under  a  strain  and  kyphosis  fol- 
lowed, so  that  his  nipples  were  on  a  level  with  the  anterior  superior 
spines  of  the  ilium.  Mental  dulness,  debility,  fatigue,  bronchitis, 
night  sweats  and  headache  harassed  him.  The  bones  of  the  face 
and  extremities  were  characteristically  enlarged.  Circumference  at 
nipples,  62  inches,  and  over  the  most  prominent  part  of  the  kyphosis 
and  pigeon  breast,  74  inches. 

Prof.  Woods  Hutchinson  has  published  an  interesting  record  of 
an  autopsy  in  a  giantess.  The  height  of  this  individual  was  6  feet 
7^  inches.  She  was  a  native  of  France  and  died  at  the  age  of  17 
in  the  United  States  quite  suddenly,  after  a  short  attack  of  grippe 
or  bronchitis,  her  illness  lasting  only  three  daj^s,  but  having  been 
preceded  by  several  years  of  failing  strength.  She  was  greatly 
emaciated,  and  this  fact  led  to  the  general  belief  that  she  had  died 
of  consumption. 

At  the  autopsy  a  remarkable  condition  of  affairs  was  observed. 
The  great  height  was  found  to  be  due  to  greatly  enlarged  extremi- 
ties, as  compared  with  the  trunk.  The  hand  was  11.25  inches  in 
length,  or  nearly  one-seventh  of  the  height.  The  foot  was  13.75 
inches  long.  The  lower  jaw  measured  6.25  inches  from  angle  to 
symphysis,  as  against  3.75,  which  is  the  normal  for  male  adults. 
The  skull  itself,  however,  measured  21^  inches  in  circumference, 
as  compared  with  the  normal  measurement  (female)  of  20  inches. 

The  genital  organs  were  deficient;  the  mammary  glands  were 
almost  completely  absent.  The  mons  veneris  and  labia  were  flat 
and  poorly  developed.  The  vagina  was  small  and  straight,  barely 
admitting  the  forefinger.  The  uterus  was  1.25  inches  long  and  ^ 
inch  broad,  about  the  size  and  shape  of  the  last  joint  of  the  little 
finger,  and  weighed  two  drachms.  The  Fallopian  tubes  were  barely 
recognizable.  The  ovaries  were  small,  granular  -  looking  masses, 
about  the  size  of  the  finger-nail,  adhering  to  the  surface  of  the 
broad  ligament.  The  skeleton  was  spongy  and  crumbling,  a  good 
example  of  osteo-porosis. 

The  skull  showed  enormous  frontal  sinuses  and  a  huge  pituitary 
fossa.  The  latter  measured  1.25  inches  in  antero-posterior  diameter, 
and  1.50  inches  transversely. 


ACROMEGALY  53 

The  author  has  examined  a  giant  now  living,  named  Henry 
Alexander  Cooper,  who  was  born  in  the  county  of  York,  England, 
on  the  12th  of  March,  i860.  He  is  seven  feet  and  five  inches  in 
height  with  boots  on,  and  the  circumference  of  his  head  is  twenty- 
five  inches.  There  is  no  prognathism,  no  exophthalmus,  and  no 
hemianopsia.  There  was  formerly  severe  headache,  and  at  one  time 
pain  in  his  eyes  with  some  blurring  of  vision  at  about  the  period  of 
greatest  growth.  The  brows  are  rather  prominent,  the  nose  large; 
the  chin,  however,  is  not  unduly  prominent,  considering  the  size  of 
the  face.  The  latter  is  of  oval  shape.  The  hands  and  feet  are  not 
disproportionate  to  the  size  of  the  skeleton.  The  abdomen  is  not 
prominent,  and  there  is  neither  excessive  thirst  nor  hunger.  The 
man  seems  to  be  losing  flesh.  It  was  not  possible  to  ascertain  his 
exact  weight.  This  giant  is  not,  therefore,  a  case  of  acromegaly. 
It  should  be  stated  that  this  man's  intellect  is  perfectly  clear,  his 
manner  pleasing,  and  his  voice  agreeable. 

I  cannot  leave  this  subject  without  referring  to  the  masterly 
description  by  Prof.  D.  J.  Cunningham  of  the  Irish  giant,  Cornelius 
McGrath.  This  individual  was  born  in  Ireland  in  1736  and  died  in 
1760,  being  23  years  old.  His  height  was  seven  feet  two  and  one- 
quarter  inches,  as  measured  by  the  skeleton  now  in  the  Anatom- 
ical and  Zoological  Museum  in  Dublin.  This,  however,  is  less  than 
the  height  of  the  skeleton  I  describe  and  less  than  that  of  Charles 
Bj^rne's  skeleton,  now  in  the  Royal  College  of  Surgeons  of  England, 
viz.,  seven  feet  seven  inches.^  The  skull  of  the  Irish  giant  has 
a  cubic  capacit}^  of  1600  cubic  centimeters;  that  of  Byrne,  1520 
cubic  centimeters;  while  mine  has  a  capacity  of  2320  cubic  centi- 
meters. I  will,  however,  reserve  comparisons  until  I  give  the 
description  of  my  case  in  full. 

It  may  be  said  before  closing  that  Virchow  is  generally  quoted 
as  believing  that  there  is  no  connection  whatever  between  the 
partial  giant  growth  which  is  seen  in  ordinary  cases  of  acromegaly 
and  general  giant  growth,  but  most  authorities,  including  L,anger, 
Cunningham,  and  W.  Hutchinson,  unite  in  holding  an  opposite 
position. 

MIXED   PRI^MATURE    AND    IMMATURE    DEVELOPMENT. 

Cases  have  arisen  which  have  suggested  that  there  is,  paradox- 
ical as  it  may  seem,  a  relation  between  gigantism  and  dwarfism. 
Such  cases  are  those  described  by  Mr.  Jonathan  Hutchinson  in  1S66 
and  by  Mr.  H.  Gilford  in  1896.  In  the  latter  case,  while  the  patient 
was  clearly  a  dwarf,  there  were  parts  that  were  more  than  full)^ 

1  Comparative  measurements  of  these  and  other  skeletons  will  be  given  later. 


54  ACROMEGALY 

developed;  and  Mr.  Gilford  was  led  by  this  case  to  the  study  of 
dwarfism  and  gigantism.  He  sees  a  close  relationship  between  these 
deviations  in  nutrition,  and  suggests  the  term  micromegaly  as 
descriptive  of  his  case  and  others  allied  to  it.  He  thinks  it  not 
impossible  that  the  cause  of  acromegaly  operating  before  birth  may 
bring  about  micromegaly;  for  many  giants  have  evidently  owed 
their  proportions  to  the  former.  May  the  one  be  the  congenital 
condition  of  the  other,  or  are  the  two  opposite  states? 

DIAGNOSIS. 

In  a  large  proportion  of  cases  the  diagnosis  of  acromegaly  is 
made  without  difficulty.  The  symptoms  are  so  characteristic  and, 
once  seen  and  recognized,  are  so  indelibly  impressed  on  the  observer, 
that  subsequent  cases  are  not  readily  overlooked  when  the  affection 
is  well  established.  It  is  obviously  important,  however,  to  recognize 
these  cases  at  the  outset,  and  if  medication  will  accomplish  any- 
thing, as  we  believe  it  may,  the  task  of  counteracting  the  disease 
will  be  the  easier. 

Without  repeating  what  has  already  been  said  in  the  preceding 
chapter  on  symptomatology  of  typical  cases,  I  will  reserve  my 
remarks  for  the  atypical  forms  and  for  some  of  the  diseases  with 
which  the  affection  may  be  confused.  As  new  diseases  become  bet- 
ter known,  it  becomes  possible  to  detect  and  classify  varieties  typical 
and  atypical,  or,  as  the  French  term  the  latter  class,  ' '  les  formes 
frustes.'"  Many  refinements  of  diagnosis  have  been  made  in  the 
case  of  other  affections;  thus  we  may  recognize  exophthalmic  goitre 
without  goitre;  tabes  may  be  diagnosticated  while  latent  and  with- 
out incoordination;  and  Chauffard  therefore  asks  why  we  may  not 
diagnosticate  acromegaly  without  hypertrophy  of  the  members. 
The  difficulty  probably  would  be  that  it  is  the  members  that  present 
the  first  objective  symptoms.  But  we  shall  probably  hear  that 
diagnosis  will  be  made  on  the  strength  of  ocular  changes,  pares- 
thesiae,  headaches,  genital  disorders  and  deficiencies,  and  hyper- 
trophies at  the  minor  terminal  points  in  the  body. 

Four  years  after  Marie  discovered  acromegaly,  he  was  able  to 
differentiate  another  affection  which  bears  a  very  strong  resemblance 
to  it,  but  which  appears  to  be  a  separate  entity.  Marie  says  of  this 
affection:  "Sous  1' influence  de  micro  -  organismes,  la  production  au 
niveau  des  lesions  de  I'appareil  respiratoire  de  substances  puruleutes 
ou  fermentees,  passant  en  suite  dans  la  circulation,  exerce  une 
action  elective  sur  certaines  parties  des  os  et  des  articulations,  pour 
determiner  les  lesions  de  Tosteo-arthropathie  hypertrophiante. " 


ACROMEGALY  55 

The  following  parallel  by  Rauzier  gives  the  differential  diagnosis 
of  the  two  affections: 


ACROMEGALY. 


PULMONARY   HYPERTROPHIC    OSTEOARTHRO- 
PATHY. 


1.  Large  stumpy  hands;  fingers  uniformly  i.  Hands  deformed;  fingers  greatly  en- 
hypertrophied,  with  preservation  of  the  pro-  larged,  club-shaped  tips;  nails  enlarged, 
portions  of  the  phalanges;  nails  small  and  lengthened  and  curved,  striated  and  cracked, 
flattened.                                                                        Hyperextension  of  the  phalanges  possible. 

2.  Great    increase  in  size    of    the    carpo-  2.  Slight  hypertrophy  of  the  heads  of  the 
metacarpal  region.                                                      metacarpals;  nearly  normal  si^e  of  the  carpo- 
metacarpal region. 

3.  Hypertrophy  of  the  wrist,  proportionate  3.  Great  deformity  of  the  wrist,  which  is 
to  that  of  the  hand,  without  deformity.                  enlarged,  swollen,  and  forms  a  considerable 

prominence  above  the  dorsum  of  the  hand. 

4.  Same  degree  of  change  in  the  feet  as  in 
the  hands. 

5.  The  lesions  are  in  the  bones  and  soft  5.  Alterations  affect  only  the  bones,  par- 
tissues  alike,                                                                     ticularly  the  epiphysis,  in  certain  joints.  The 

soft  parts  do  not  partake  in  the  enlargement 
affecting  the  bones.    .Slight  edema. 

6.  Kj'phosis,  common  symptom  —  cervico-  6.  K3'phosis  not  so  frequent  and  late  in 
dorsal.                                                                             onset.    Scoliosis  frequent. 

7.  Great  hypertrophy  and  exaggeration  of  7.  Lower  maxilla  normal.  Occasional 
the  curves  of  the  lower  jaw.                                      thickening  of  the  alveolar   border   of    the 

superior  maxilla. 

8.  Obscure  pathologj';   probably  defect  of  8.  Pulmonary  origin, 
nutrition. 

We  recognize  the  same  agencies  in  the  production  of  the  w^ell 
known  ' '  club-fingers ' '  of  tuberculosis.  The  circulation  carries  the 
microbes  and  their  products  to  the  extremities  of  the  fingers,  where 
they  react  on  the  bones  and  surrounding  tissues  to  produce  hyper- 
trophy. 

The  question  has  been  raised  whether  hypertrophic  pulmonary 
osteoarthropathy  is  a  separate  disease  or  a  transition  stage  between 
the  rheumatic  arthropathies  and  acromegaly.  We  are  not  in  a  posi- 
tion to  determine  all  these  inter-relations;  but  no  doubt  further 
observations  will  soon  clear  up  the  different  dystrophies  of  this 
class,  if  we  maj'-  judge  by  the  great  advances  made  in  the  last 
decade. 

Myxedema. — We  have  here,  as  in  acromegaly,  enlargement  of 
the  face  and  limbs,  with  the  difference  that  in  myxedema  the  hyper- 
trophy affects  the  soft  tissues  exclusively;  the  skin  is  greatly 
thickened,  of  a  brawny  nature  and  a  ^''ellowish  or  waxy  color, 
and  is  not  movable  on  the  underlying  structures;  while  in  acro- 
megaly the  hypertrophy  affects  all  the  tissues  and  the  skin  is  more 
flexible  and  movable.  It  is  customary  to  speak  of  the  face  of 
myxedema  resembling  the  full  moon,  because  of  its  puffiness. 
The  face  in  acromegaly,  on  the  other  hand,  is  elongated.  In 
myxedema  the  thyroid   is  usually  atrophied,   mental  weakness   is 


56  ACROMEGALY 

common,  bodily  stature  is  small,  and  the  disease  is  more  common 
in  women  than  in  men.  There  is  no  prognathism,  kyphosis  or 
symptoms  referable  to  an  enlarged  pituitary  body.  (See  Dr. 
Norman  Dalton's  case  of  combined  myxedema  and  acromegaly.) 

Osteitis  Deformans  (Paget's  Disease). — This  is  accompanied  by 
curvature  of  the  long  bones  of  the  skeleton,  especially  the  femora 
and  tibiae.  The  skull  is  broad  at  the  top  and  the  entire  contour  of 
the  head  is,  in  general,  that  of  a  triangle  with  the  base  upward.  In 
myxedema  the  face  is  round,  while  in  acromegaly  the  face  shows  a 
distinct  oval.  Osteitis  deformans  has  never  been  known  in  patients 
under  forty  years  of  age. 

In  acromegaly,  as  Marie  puts  it,  the  osseous  changes  are  seen 
in  the  extremities  of  the  bones  and  the  bones  of  the  extremities.  In 
Paget's  disease,  on  the  other  hand,  the  shafts  of  the  bones  show 
characteristic  changes,  such  as  bowing  of  the  tibiae  and  femora,  or 
even  of  the  humerus  and  forearm.  In  osteitis  deformans  the  cranial 
bones  are  chiefly  affected,  while  in  acromegaly  the  facial  bones 
undergo  hypertrophy. 

The  skeletal  changes  in  acromegaly  tend  to  take  place  s^^m- 
metrically,  while  in  osteitis  deformans  a  single  bone,  such  as  the 
tibia  or  femur,  may  be  first  attacked,  and  after  a  considerable 
interval  the  corresponding  bone  of  the  opposite  side  presents  similar 
changes;  but  the  bone  originally  involved  will  usually  present  a 
greater  hypertrophy  than  the  bone  secondarily  involved. 

Elephantiasis. — This  is  also  usually  an  asymmetrical  affection. 
The  hypertrophy  involves  the  entire  member.  The  lower  jaw  and 
spine  are  not  involved.  The  skin  is  indurated,  very  thick,  dry,  and 
difficult  to  move.  Ocular  symptoms  are,  of  course,  absent.  (See 
Lombroso's  case  and  the  case  of  the  Hagner  brothers,  described  by 
Arnold,  for  elephantiasis.) 

Chronic  Rheimiatism.  — This  has  been  the  diagnosis  in  many 
cases  seen  in  the  early  stages.  In  the  case  of  giants  that  have  had 
acromegaly,  rheumatic  pains  are  noted  and  also  what  were  naturally 
termed  "growing  pains."  The  "Irish  Giant"  was  subjected  to 
baths  in  salt  water  for  symptoms  of  this  nature.  The  pains  of 
rheumatism  are  chiefly  in  the  larger  joints  and  are  accompanied 
often  by  grating  and  unilateral  wasting.  The  face  escapes.  There 
is  usually  a  history  of  an  acute  attack,  and  cardiac  symptoms  ensue. 

It  has  been  remarked  that  disturbances  simulating  acromegaly 
may  also  occur  in  the  course  of  tabes.  Partial  acromegaly,  or  more 
properly  partial  hypertrophies,  occur.  They  are,  as  far  as  I  have 
seen,   congenital,   involving   one   side,   and  stationary.     Thej^   are 


ACROMEGALY  57 

variously  designated  as  macrodactyly,  macropody,  hypertrophy  of  a 
single  member  or  of  one-half  of  the  body.  If  they  have  anything 
to  do  with  acromegaly,  we  must  look  for  it  in  some  prenatal  condi- 
tion not  yet  understood. 

ROENTGEN   PHOTOGRAPHY    IN   THE    DIAGNOSIS    OF    ACROMEGALY. 

This  latter-day  means  of  diagnosis  has  been  used  by  Marinesco, 
who  has  submitted  the  hands  of  four  subjects  of  acromegaly  to 
Roentgen  photography,  as  follows:  Three  of  the  patients  belonged 
to  the  massive  type  described  by  Marie,  while  the  fourth,  a  woman 
of  33,  was  of  the  gigantic  type.  In  the  first  case,  a  man  aged  55, 
of  the  massive  type,  whose  affection  was  of  eleven  years'  standing, 
the  skiagraphs  showed  a  marked  hypertrophy  of  the  metacarpal 
bones  and  phalanges.  This  hypertrophy  was  uniform;  it  was  merely 
an  exaggeration  of  the  normal  state.  The  epiphyses  and  apophyses 
of  the  last  phalanx  were  hypertrophied  and  measurements  were 
readily  made  from  the  skiagraph.  In  the  third  patient,  aged  33 
years,  who  presented  the  giant  form  of  the  disease,  of  eight  years' 
duration,  the  skiagraph  showed  that  the  hypertrophy  of  the  soft 
parts  was  much  less  than  in  the  first  case.  In  the  fourth  patient, 
aged  33,  an  example  of  the  massive  type  which  was  of  at  least  seven 
years'  duration,  the  skiagraph  revealed  a  hypertrophy  of  the  extrem- 
ities of  the  phalanges  and  of  the  metacarpals.  In  this  case  the 
distance  from  the  metacarpo-phalangeal  articulation  to  the  extremity 
of  the  last  phalanx  was  11  centimeters  2  millimeters.  There  was 
hypertrophy  in  length  and  in  thickness.  It  was  thus  easj'  to 
demonstrate  the  clinical  type  to  which  a  case  belongs  by  noting  the 
relation  between  the  hypertrophy  of  the  soft  parts  and  the  bones. 
In  acromegaly  of  the  massive  type,  the  hypertrophy  of  the  soft 
parts  is  much  greater  than  in  the  case  of  acromegaly  of  the  giant 
type.  Marinesco  also  examined  a  case  of  erythromelalgia  in  the 
same  manner,  and  failed  to  find  any  lesions  of  the  skeleton,  which 
shows  that  this  affection  has  no  relation  to  acromegal3^ 

In  Sir  William  Broadbent's  case  the  skiagraphs  showed  that  the 
hypertrophy  was  wholly  in  the  soft  parts. 

TREATMENT. 

The  treatment  of  acromegaly  is  more  encouraging  than  the  brief 
references  to  it  in  the  text-books  would  lead  us  to  suppose.  We 
understand,  of  course,  that  the  palliative  or  symptomatic  treatment 
is  of  great  importance  in  improving  the  general  comfort  of  the 
patient.     The  intense  headaches,  the  paresthesiae,  the  pains,  which 


58 


ACROMEGALY 


Fig.  25. — Skiagraph  of  right  hand  from  case  of  acromegalj'  (Osborne). 


ACROMEGALY  59 

in  many  cases  have  been  considered  rheumatic,  and  the  general 
depression  of  spirits,  may  be  treated  with  more  or  less  success  by 
various  drugs  and  measures  directed  to  the  nervous  system.  Chief 
among  these  we  may  mention  phenacetine,  antipyrin,  iodides,  bro- 
mides, and  caffeine.  Headaches  that  are  refractory  have  been 
greatly  mitigated  by  the  use  of  cannabis  indica  and  acetanilid.  The 
pains  in  the  extremities  are  sometimes  benefited  by  the  use  of  code- 
ine or  morphine.  Iron,  arsenic  and  strychnine  have  their  place  in 
giving  tone  to  the  enfeebled  muscles  of  the  later  stages. 

Glycosuria,  if  it  be  present,  also  demands  attention  and  should 
be  treated  by  a  suitable  diet,  by  the  use  of  salicylates,  alkalies, 
codeine,  or  other  drugs  suited  to  that  particular  condition. 

It  is,  however,  in  the  use  of  animal  extracts  that  the  general 
treatment  of  the  disease  will  probably  receive  the  greatest  benefit. 
While  much  discussion  has  attended  the  explanation  of  the  action  of 
thyroid  extract  and  pituitary  extract,  the  fact  remains  that  these 
agents  are  being  used  more  and  more  in  diseases  of  the  nervous  sys- 
tem, and  in  the  case  of  acromegaly  thyroid  extract  seems  to  be  the 
favorite.  It  is  remarkable,  however,  that  so  many  cases  elaborately 
recorded  in  all  other  respects  are  destitute  of  any  note  whatever  as 
to  treatment. 

Brown-Sequard  was  the  first  to  advocate  the  use  of  thyroid  and 
other  animal  extracts  in  acromegaly.  In  a  communication  to  La 
Societe  de  Biologic  on  May  20,  1893,  he  said:  "  Ce  sont  les  liquides 
retires  de  la  rate  de  la  thyroide  et  de  la  moelle  des  os,  qui  paraissent 
certainement  devoir  posseder  le  plus  de  puissance  contre  cette  terri- 
ble maladie." 

Although  much  ridicule  was  indulged  in  by  the  medical  profes- 
sion and  the  laity  when  Brown-Sequard  first  enunciated  his  belief  in 
the  rationale  and  efficacy  of  extracts  made  from  various  animal 
tissues,  belief  in  their  use  is  steadily  gaining  ground.  Thyroid 
extract,  in  particular,  has  assumed  what  seems  to  be  a  permanent 
place  in  the  treatment  of  various  diseases,  notably  myxedema,  and 
its  use  in  obesity,  mental  troubles  and  other  affections  is  rapidly 
spreading.  The  use  of  hypophysis  cerebri  is  not  mentioned  by 
M.  Bra  in  his  elaborate  work  on  animal  extracts,  and  as  far  as  I 
know  was  not  mentioned  by  Brown-Sequard.  The  latter  employed 
the  hypodermic  method,  and  his  plan  involved  the  use  of  "injec- 
tions quotidienne  et,  a  parts  egale,  de  liquide  de  rate  et  -de  moelle 
des  OS,  et  d'adjoindre  au  besoin  a  ces  deux  liquides,  le  liquide  orchit- 
ique."  I  do  not  know  of  any  cases  in  which  this  plan  of  therapy 
has  been  carried  out. 


6o  ACROMEGALY 

Cases  have  been  treated  with  thyroid  extracts  by  the  following 
authors:  Bramwell,  Benson,  Sanger  Brown,  Bruns,  S.  Solis-Cohen, 
Costanzo,  Eschle,  Eshner,  Jeffrey,  Mendel,  Mosse,  Middleton,  Mur- 
ray, R.  N.  Parsons,  J.  J,  Putnam,  Schultze,  Unna  and  Vinke,  Sears, 
Comini,  Witmer. 

Bruns'  patient  was  a  woman,  aged  24,  who,  after  an  abortion  in 
her  first  pregnancy,  experienced  vague  pains  and  forms  of  pares- 
thesia in  the  hands  and  feet,  which  were  noticed  to  become  gradually 
enlarged.  Two  years  later  she  presented  a  typical  picture  of  acro- 
megaly, with  enlargement  of  bones  and  soft  parts  of  the  face; 
marked  thickening  of  bones  of  trunk,  especially  the  clavicles;  hands 
and  feet  enormously  enlarged ;  patient  extremely  nervous  and 
excitable,  sleeping  very  badly;  suffering  from  almost  constant  head- 
ache; vague  pains  and  abnormal  sensations  in  extremities,  prevent- 
ing her  from  doing  any  fine  work.  Tabloids  of  thyroid  extract 
(quantity  unknown)  were  given  in  increasing  doses  until  four  were 
taken  per  diem.  The  enlargement  of  parts  persisted,  but  the 
improvement  in  subjective  symptoms  was  striking;  the  nervous 
excitability  rapidly  diminished,  the  patient  slept  well,  and  the 
headache  disappeared;  the  pains  in  the  extremities  also  vanished, 
and  the  patient  was  able  to  resume  the  finest  work. 

Benson's  and  Mosse 's  cases  treated  with  thyroid  extract  also 
gave  good  results.  In  the  latter  the  chief  benefit  was  observed  in 
the  mental  symptoms.  The  patient  afterwards  died,  and  a  large 
sarcoma  of  the  hypoph3-sis,  weighing  thirty -six  grammes,  was 
found. 

In  a  case  recorded  by  J.  J.  Putnam,  thyroid  powder  in  doses  of 
fifteen  grains  every  second  day  made  great  improvement.  The 
hands  and  feet  diminished  steadilj^  in  size,  so  that  the  patient 
(a  woman)  at  the  end  of  three  weeks  was  able  to  resume  work  with 
her  hands,  and  after  further  treatment  could  ' '  wear  boots  that  she 
could  not  get  on  at  all  when  her  symptoms  were  at  their  height." 

In  Feliciano  Costanzo' s  case  remarkable  improvement  followed 
the  use  of  the  thyroid  extract  for  a  period  of  eighty -one  days, 
including  a  cessation  of  two  weeks  on  account  of  physiological 
symptoms  due  to  the  drug  (pulse  140,  vomiting,  temperature  39-40° 
C,  pain  in  the  head  and  limbs).  The  dose  was  three  teaspoon fuls 
administered  by  the  mouth  three  times  a  day. 

Before  After 

treatment.  treatment. 

Right  hand — Circumference  of  thumb 7.5  cm.  7     cm. 

Circumference  of  index  finger — 

First  phalanx 7.5  cm.  7     cm. 

Second  phalanx 7.5  cm.  5     cm. 

Third  phalanx 6.2  cm.  6     cm. 


ACROMEGALY  6i 

Before  After 
treatment,  treatment. 
Circumference  of  middle  finger- 
First  phalanx S     cm.  7     cm. 

Second  phalanx 7-5  cm.  6     cm. 

Third  phalanx 6     cm.  5-5  cm. 

Left  foot— Circumference  of  great  toe 12.5  cm.  9.5  era. 

Circumference  of  second  toe 7.5  cm.  6     cm. 

Circumference  of  third  toe 7.5  cm.  6     cm. 

Circumference  of  fourth  toe 8     cm.  6.5  cm. 

Circumference  of  fifth  toe 7     cm.  5     cm. 

Circumference  of  left  foot 26     cm.  24     cm. 

Body  weight 67     kg.  59     kg. 

It  is  thus  evident  that  to  obtain  the  best  results  thyroid  extract 
should  be  pushed  to  its  physiologic  and  even  toxic  effect. 

Vinke  treated  his  patient,  a  woman  of  5 1  years,  with  both  thyroid 
extract  and  pituitary  extract,  as  follows:  During  the  first  two 
months  she  took  one-half  grain  of  thyroid  extract  three  times  a  day. 
One  grain  of  this  extract  represents  ten  grains  of  the  fresh  gland. 
During  the  third  and  fourth  months,  desiccated  pituitary  bodies 
were  given,  about  one  and  a  half  grains  three  times  a  day.  During 
the  last  month  a  combination  of  both  extracts  was  administered, 
four  grains  of  desiccated  pituitary  bodies  and  one -half  grain  of 
thyroid  extract  a  day.  By  comparing  the  measurements  at  the 
beginning  of  the  treatment  and  five  months  later,  it  will  at  once  be 
seen  that  there  is  a  decided  decrease  in  size. 

Pituitary  extract  has  been  used  by  the  following:  D'Esterre, 
Bard,  Bramwell,  Broadbent,  Dodgson,  Marinesco,  Mendel,  Murray, 
Ransom,  Rolleston  and  Vinke,  Eshner,  Dercum,  Thomas,  Schultze, 
and  Osier. 

Marinesco  has  used  pituitary  extract  in  three  cases.  The  first 
two,  a  woman  of  53  years  and  a  man  of  54,  belonged  to  the  massive 
type;  the  third  was  a  woman  of  30  years,  of  the  gigantic  type.  In 
the  first  case  there  were  such  violent  headaches  that  suicide  was 
contemplated.  The  pain  was  soon  relieved,  but  nausea  set  in,  and 
on  an  increase  of  the  remedy  there  was  colic  and  diarrhea.  There 
was  improvement  while  taking  four  tabloids  daily,  but  before  long 
the  headaches  returned.  The  variations  of  the  pulse  were  not  such 
that  a  definite  conclusion  could  be  drawn  from  its  influence  on  the 
circulation.  The  urine  was  increased  from  a  liter  to  a  liter  and 
a  half  and  even  two  liters  daily.  No  change  was  noted  in  the  size 
of  the  limbs. 

A  second  case,  treated  by  Marinesco  with  pituitary  extract  in 
doses  gradually  increased  from  one-half  a  tabloid  to  four  tabloids 
daily,  gave  at  first  no  especial  symptoms,  subjective  or  objective; 
but  a  gradual  relief  from  headache  followed  in  two  weeks.     The 


62 


ACROMEGALY 


pains  in  the  hands  became  less  and  their  movements  more  free.  In 
two  months  it  was  possible  to  s-ax  that  the  soft  parts  involved  were 
less  swollen  than  before  the  treatment  was  instituted.  The  head- 
aches, the  paresthesias  in  the  hands  and  the  pains  in  the  lower 
members  were  lessened.  The  pulse  varied  from  60  to  80,  and  the 
urine  reached  1300  grammes. 

In  Marinesco's  third  case,  a  diabetic,  the  urine  was  increased 
quickly  from  sixteen  liters  to  twenty-one  liters.  The  bodily  weight 
at  first  declined  and  then  increased. 

Sir  W.  Broadbent  treated  one  case  with  pituitary  extract  wnth 
some  improvement  of  mental  condition,  although  in  this  case  it  was 
believed  that  the  improvement  maj^  have  been  referable  to  the  relief 
of  the  excessive  constipation. 

It  is  probable  that  a  combination  of  pituitary  and  thyroid 
extracts  w^ould  be  of  service  in  cases  where  both  of  these  structures 
are  diseased.  It  is  not  out  of  place  to  cite,  in  this  connection,  the 
remarkable  effect  which  thyroid  extract  produces  when  given  in 
the  treatment  of  obesity.  Out  of  145  recorded  cases  it  produced  a 
decided  effect  in  96  per  cent. ;  the  loss  of  weight  being  in  respect  to 
fat,  w^atery  constituents,  and  albuminoids.  Thus  we  see  that  over- 
growth, entirely  independent,  as  far  as  we  know,  of  any  change  in 
the  hj^pophysis,  also  responds  to  this  medication. 


Name. 

Amount. 

Result— Pituitary  Treatme:j^t. 

No  result;  rabbit's  gland,  subcutaneouslv. 

Improved;  thyroid  treatment  failed. 

Unimproved:  thvroid  treatment  improved. 

Broadbent  &  Dodgson's... 

Improved  mentallv. 

Unimproved. 

2  grs.  t.  d. 

Lost  ei^ht  pounds. 

Unimproved. 

Marinesco's  (ist) 

4  tabloids  daily. 
^  to  4  tabloids  daily. 

Greatly  improved. 
Greatlv  improved. 

Marinesco's  (3d) 

MendePs 

Slightlv  improved. 

15  grs.  dailj'. 

Improved;  failed  to  improve  under  thyroid. 

Unimproved. 

Rolleston's  (ist) 

RoUeston's  (2d) 

5  grs.  b.  d. 
5  grs.  b.  d. 

Unimproved;    used  thyroid  extract  simul- 
taneously. 
Improved  as  to  headache;  used  thyroid  ex- 

tract simultaneously. 
Worse;  heart  disturbed. 

No  result;  effect  unpleasant. 

I  to  4  grs.  t.  d. 
4  grs.  t.  d. 

Greatly  improved;    alone    and    combined 

with  thvroid. 
Unimproved  at  two  months;  slightlv  better 

at  three  months. 

French  writers  have  questioned  how  much  the  influence  of  sug- 
gestion may  have  to  do  with  the  beneficial  results  noted  in  cases  of 
nervous  diseases  treated  with  the  organic  extracts.  It  is  naturally 
diflScult  to  settle  such  questions  conclusively. 


ACROMEGALY  63 

Marinesco  formulates  two  propositions: 

1.  Tablets  of  pituitary  glaud  exert  in  acromegaly  an  "elective 
action,"  particularly  upon  the  cells  of  the  tumor,  which  have  pre- 
served their  integrity. 

2.  They  act  upon  the  intracranial  pressure,  or  rather  upon  the 
vessels  of  the  pituitary  tumor. 

The  observed  effects  might  be  explained  by  either  proposition. 
The  remedy  may  be  able,  when  introduced  into  the  circulation,  to 
excite  the  diseased  hypophysis  or  aid  its  action  and  thus  bring  about 
a  lessening  of  the  disturbances. 

Or,  on  the  other  hand,  which  the  experiments  of  E.  Schaefer 
and  Oliver  tend  to  prove,  the  extract  of  pituitary  gland  has  a  vaso- 
motor action  by  which  the  constriction  of  the  vessels  of  the  highly 
vascular  pituitary  tumor  would  be  able  to  exert  a  contraction  of 
that  body,  and  consequently  a  modification  of  the  intracranial  ten- 
sion, a  process  which  would  readily  explain  the  relief  from  head- 
ache. They  found  a  rapid  and  considerable  rise  of  blood-pressure, 
due  to  a  direct  action  on  the  arterioles  and  probably  on  the  heart 
muscle. 

These  questions  are  still  unsettled,  and  we  remain  in  ignorance 
of  the  mechanism  of  the  production  of  acromegaly. 

E.  Schaefer  has  shown  that  the  action  of  thyroid  extract  is  to 
diminish  blood-pressure,  while  pituitary  extract  greatly  increases  the 
pressure,  as  I  have  stated. 

Isaac  Ott  has  made  a  contribution  to  this  subject  in  a  "  Note  on 
Animal  Extracts,"  published  in  1896.  His  experiments  were  made 
upon  rabbits,  and  he  found,  as  did  Schaefer  and  Oliver,  that  the 
thyroid  lowered  the  blood-pressure,  but  with  this  difference:  that  it 
lowered  the  heart  beats,  even  when  he  used  cold  filtered  infusion  of 
thyroid.  This  lowering  of  the  heart  beat  ensued  when  the  vagi 
were  cut  or  when  their  peripheral  encis  were  paralyzed  by  atropine. 
Thus  it  is  probable  that  the  drug  acts  upon  the  heart  itself  and  thus 
lowers  the  cardiac  beat.  The  fall  of  pressure  is  not  due  to  a  paral- 
ysis of  the  main  vasomotor  center,  for  the  arterial  tension  falls  quite 
as  readily  when  the  cord  is  cut.  The  cold  filtered  infusion  of  the 
pituitary  gland  produced  a  rise  of  blood-pressure  and  a  fall  of  pulse. 
The  subcutaneous  injection  of  pituitary  powder  caused  hardly  any 
rise  of  temperature. 

Szymonowicz,  in  two  experiments,  obtained  a  slight  fall  of 
pressure  and  a  quickened  heart  beat.  Mairet  and  Bosc  noted  very 
slight  physiological  effects  from  the  use  of  pituitar}'  extract  beyond 
a  slight  rise  of  temperature  and  depression  with  some  digestive  dis- 
turbance. 


64 


ACROMEGALY 


Prof.  W.  H.  Howell  has  injected  into  the  circulation  of  dogs 
extracts  of  the  hypophysis  of  sheep.  They  were  made  in  normal 
saline,  or  in  glycerin,  followed  by  dilution  in  normal  saline.  It  was 
found  that  the  extract  of  the  glandular  lobe  had  little  or  no  per- 
ceptible effect.  The  extract  of  the  infundibular  lobe  had  a  distinct 
and  remarkable  effect  on  the  heart -rate,  which  was  slowed  and 
augmented  in  force.  At  the  same  time  the  blood-pressure  rises  to  a 
considerable  extent,  owing,  apparently,  to  a  peripheral  constriction 
of  the  blood-vessels.  The  rise  is  followed  by  a  temporary  fall  of 
pressure,  during  which  the  heart-rate  may  be  increased.  When  the 
vagi  are  previously  cut  the  slowing  of  the  heart  is  much  less  marked. 

author's  e;xpe:rimknts. 

Results  of  the  experiments  made  upon  animals  in  the  laboratory 
of  Parke,  Davis  &  Co.  by  Dr.  B.  M.  Houghton,  at  the  author's 
request.     Three  tracings  were  taken. 

The  extract  was  made  so  that  one  cubic  centimeter  represents 
one  gramme  of  the  pituitary  body.  Alcoholic  and  aqueous  extracts 
were  made;  in  the  case  of  the  alcoholic  extract  it  was  evaporated  at 
low  temperature  and  taken  up  with  water. 


Fig.  26.— Effect  of  injection  of  filtered  infusion  of  pituitary  gland  (Ji  grain).    Star  denotes  moment  of 
injection.    Read  from  right  to  left.     (Ott.) 


ACROMEGALY  65 


iO£o.vv/^ 


I 


'%^^^^,p^^^rJ'^^^^^v*^N^'V^'V^ 


Fig.  27— Action  of  the  extract  of  pituitary  gland  on  the  circulation  (Hinsdale). 

Experimeiit  i.  —  Dog;  weight,  9725  grammes.  Injected  intra- 
venously one  cubic  centimeter  of  the  aqueous  extract  of  fresh 
pituitary  gland.  There  was  no  immediate  change  in  pressure,  but 
at  the  end  of  one  hour  there  was  a  gradual  fall  of  ten  millimeters. 

Experiment  ^.—Rabbit.  Blood-pressure  experiment.  Aqueous 
extract  of  pituitary  body  injected  intravenously. 

Amount 

injected.  Blood-pressure. 

Normal,  83  mm.  Hg. 

I    Cc      Rose  to  89  mm.  Hg.;  fell  to  80  mm.  Hg. 

"c    Cc Rose  to  89  mm.  Hg.;  remained  at  87  mm.  Hg 

'c    Cc Quick  rise  to  100  mm.  Hg.;  fell  to  86  mm.  Hg. 

25  Cc".'. Gradual  rise  to  96  mm.  Hg.;  fell  to  87  mm.  Hg. 

i'      Cc  Very  gradual  fall  to  83  mm.  Hg. 

i".      Cc'.' Quick  rise  to  98,  finally  to  loi  mm.  Hg. 

Experiment  3.— ^'ah^A'i.  Blood-pressure  experiment.  Alcoholic 
extract  of  pituitary  body  injected  intravenously. 

Amount 

injected.  '  Blood-pressure. 

Normal,  90  mm.  Hg.  •      .       r  n  * 

1  Cc Immediate  rise  to  loi  mm.  Hg.;  after  ten  minutes  tell  to 

82  mm.  Hg. 

2  Cc Rose  to  89  ram.  Hg.;  gradual  fall  to  79  mm.  Hg. 

2  Cc!!....." Gradual  fall  to  75  mm.  Hg. 

4  Cc Rise  to  85  mm.  Hg. 

2  Cc Gradual  fall  to  77  mm.  Hg. 

Experiment  i  shows  a  slight  fall  in  pressure. 

Experiment  2  shows  a  primary  rise,  falling  afterward  to  about 
normal. 

Experiment  3  shows  a  primary  rise,  falling  afterward  13  mm. 
Treatment  by  Mercury  and  Iodides. — In  a  case  in  which  there  was 
no  evidence  of  syphilis,  antisyphilitic  treatment  was  adopted  by 
Schlesinger.  There  had  been  ptosis,  complete  paralysis  of  the 
oculo-motor  nerve,  and  gray  atrophy  of  the  papilla  with  temporal 
hemianopsia  and  contraction  of  the  preserved  half  of  the  visual 
field. 

The  ptosis  disappeared.  The  paralysis  of  the  third  pair  was 
relieved,  and  the  visual  field  became  normal,  except  for  a  scotoma 
for  blue  in  the  left  eye.     The  papilla  became  nearly  normal. 

Operative  Treatment.— 't\x\&  has  been  instituted  in  three  cases, 
viz.,  those  of  Caton,  I^ynn  Thomas,  and  Hare.    In  the  first  instance 


66  ACROMEGALY 

Mr.  Paul  was  asked  to  operate,  and  in  February,  1893,  he  removed 
a  portion  of  the  right  temporal  bone  to  the  extent  of  about  three 
superficial  inches.  The  brain  was  found  in  a  state  of  great  tension; 
it  did  not  pulsate  at  all  and  bulged  outward  as  much  as  the  dura 
allowed.  From  the  time  of  operation  the  intense  neuralgic  pain 
ceased,  but  the  blindness,  which  was  almost  complete,  soon  became 
absolute.     Death  ensued  three  months  later. 

In  the  case  of  Thomas  the  skull  was  opened  to  the  extent  of 
three  by  four  inches  on  the  left  side.  The  bone  was  thickened 
and  softer  than  normal.  The  patient  is  said  to  have  been  trans- 
formed "from  being  a  miserable  imbecile  into  a  useful,  intelligent 
being."  The  headache  was  cured  and  power  was  restored  to  the 
bladder. 

Hare's  case  was  operated  upon  for  the  relief  of  intense  neuralgia. 
Professor  Keen  resected  the  following  nerves:  The  supra  -  orbital, 
supra  -  trochlear,  auriculo- temporal,  auricularis  magnus,  occipitalis 
major  and  minor.     No  improvement  followed,  however. 

ACROMEGALY, 
XX.,  aged  30;  single;  English;  by  occupation  a  bookkeeper.^ 
Family  history  negative.  Previous  history:  Excepting  the  usual 
diseases  of  childhood,  the  patient  had  always  enjoyed  good  health 
until  five  years  ago,  when  he  is  reported  to  have  had  pleurisy.  He 
expectorated  blood  for  one  week.  In  the  spring  of  1891  he  fell 
about  twenty  feet,  sustaining  a  severe  scalp  wound  in  the  occipital 
region  and  a  contusion  of  the  back.  In  1893  patient  was  in  good 
health,  weighing  about  175  pounds.  He  wore  a  No.  7  hat,  a  No. 
7^  glove,  and  a  No.  7}^  shoe.  He  was  not  seen  by  his  relatives 
until  three  years  later,  when  he  wore  a  No.  8)^  hat,  a  No.  11  shoe, 
and  had  to  have  his  gloves  made  to  order.  His  weight  at  the  time 
was  about  250  pounds.  Some  time  between  1893  and  1896  the 
patient  developed  acromegaly  and  was  treated  for  it  in  Chicago. 
The  course  of  his  disease  is  said  to  have  been  arrested  under  treat- 
ment. About  six  months  ago  the  patient  was  treated  for  syphilis. 
His  symptoms  disappeared  shortly  after  medication  commenced. 
Two  months  ago  the  patient's  right  eye  began  to  trouble  him,  and 
he  is  said  to  have  been  treated  for  syphilitic  iritis.  One  month  ago 
the  eye  was  still  in  bad  condition.  About  this  time  his  friends 
began  to  suspect  him  of  using  narcotics.  He  slept  very  little  at 
night,  but  was  drowsy  at  odd  intervals  during  the  day.  Recently 
the  patient  has  eaten  very  little  on  account  of  nausea  and  vomiting, 
but  has  been  thirsty  all  the  time.  Thinking  that  his  thirst  was  due 
to  atropine  that  drug  was  omitted  by  his  physician  and  duboisine 
used  instead  for  his  iritis. 

1  The  notes  of  this  case  were  kindly  sent  to  the  author  by  Dr.  S.  Baruch,  of  New  York. 
Dr.  Harlow  Brooks,  who  made  the  autopsy,  subsequently  published  an  account  in  the  New 
York  Medical  Journal. 


ACROMEGALY  67 

Patient's  mental  condition  has  been  irritable  since  May,  1896. 
He  is  a  steady  and  heavy  drinker. 

Present  condition:  Fairly  well  nourished;  tongue  coated,  brown, 
and  dry;  skin  congested;  extremities  cold;  appears  to  be  in  a  stu- 
porous condition,  but  answers  questions;  is  suffering  with  dyspnea; 
heart  enlarged,  apex  beat  diffuse,  no  murmurs;  lungs  showed  dul- 
ness,  subcrepitant  rales  in  left  axillary  line;  pulse  feeble;  abdomen 
slightly  distended;  liver  dulness  normal;  left  pupil  about  normal, 
reacts  to  Hght;  right  pupil  dilated  and  does  not  react  to  light; 
exophthalmus;  haziness  of  right  cornea  and  conjunctiva  injected 
around  cornea;  has  myopic  astigmatism  O.D.  —  .50  cyl.  1.50  ax.  15 
deg.  O.S.  —  .25  cyl.  1.35  ax.  165  deg.;  peculiar,  sweetish  odor  to 
breath;  hands  and  fingers  somewhat  thickened;  ends  of  fingers 
slightly  clubbed;  cheek  bones  prominent;  end  of  nose  enlarged;  a 
small  furuncle  on  right  side  over  shoulder;  temperature  99.2°;  pulse 
120;  respiration  30;  urine,  straw,  clear,  acid,  1.023,  albumen  two 
per  cent.,  sugar  yj^  per  cent. 

Treatment.— Vni  to  bed,  milk  diet.  Given  seven  minims  majen- 
die  at  11.20  a.m. 

2.15  P.M.  Catheterized  and  thirty-three  fluidounces  urine  ob- 
tained, examined  as  above. 

2.45  P.M.  Is  in  a  marked  stupor.  Given  castor  oil  two  ounces, 
with  four  ounces  water. 

4  P.M.  Temperature  101°,  pulse  132,  respiration  26.  Is  restless 
and  shouting  out.     Given  liquid  majendie  7>^  minims. 

6.30  P.M.     Five  ounces  urine  obtained  by  catheter. 

8  P.M.  Is  in  stuporous  condition,  completely  unconscious,  pulse 
very  feeble.  Given  strychnine  sulphate  ^  grain  hypodermically. 
Temperature  103.8°,  pulse  128,  respiration  38. 

8.15  P.M.     Died  (December  2,  1896). 

Circumference  of  head  at  level  of  eyebrows 23^4  inches 

Circumference  of  head  at  subniento-bregmatic 27 


inches- 


>mental 28^  inches. 

Breadth  of  base  of  nose. 
Breadth  across  alae. 


Circumference  of  occipito-: 

154  inches. 

2     inches. 

"'■  '.  r        ,,  17     inches. 

Circumference  01  neck ' 

Circumference  of  right  elbow ^^      inches. 

Right.  Left. 

Circumference  of  wrist 75<  inches.  7     inches. 

Circumference  of  hand  at  knuckles 10^  inches.  io'4  inches. 

Circumference  of  base  of  thumb 3^  inches.  s'/s  inches. 

Circumference  of  last  phalanx  of  thumb yA  inches.  3K  inches 

Length  of  middle  finger  from  articulation  of  metacarpus AV2  inches.  4-7s 

Circumference  of  middle  finger SJ^i  inches.  s/s 

Length  of  forefinger 4     inches.  4'^ 

Circumference  of  forefinger zA  inches.  3H 

Length  of  ring  finger 4K  inches.  4/2 


inches, 
inches, 
inches, 
inches, 
inches. 


68  ACROMEGALY 

Right.  I.eft. 

Circumference  of  ring  finger 3     inches.  3     inches. 

Length  of  little  finger 3^  inches.  33^  inches. 

Circumference  of  little  finger 2^  inches.  2^  inches. 

Circumference  of  groin 20^  inches.  2oJ^  inches. 

Circumference  of  knee 15J4  inches.  16     inches. 

Circumference  of  calf  14     inches.  14^  inches. 

Circumference  of  ankle loj^  inches.  10%  inches. 

Circumference  across  foot 10^  inches.  10     inches. 

Breadth  across  foot 4%  inches.  45^  inches. 

Length  of  great  toe 2j^  inches.  2%  inches. 

Circumference  of  great  toe 4^  inches.  4^  inches. 

General  Description.  —  Head  large,  lips  thick;  eyebrows  promi- 
nent and  one  hanging;  eyelids  thick  and  heavy;  cheek  bones 
prominent;  space  between  the  eye  and  malar  bone  one  plane;  nose 
short,  thick,  and  fiat,  point  of  nose  blunt  and  almost  globular; 
tongue  broad  and  thick;  teeth  good;  ears  large  and  prominent;  neck 
short;  shoulders  broad  and  square;  arm  and  forearm  normal  in 
appearance  to  wrist;  bones  at  wrist -joint  enlarged;  hand  short, 
broad,  and  thick;  ends  of  fingers  squared;  nails  broad,  square,  flat, 
and  curved  at  ends,  but  not  thickened;  base  of  digits  broad  and  flat; 
thighs  and  pelvis  well  formed;  knee-joints  prominent;  lower  epi- 
physis of  tibia  and  fibula  enlarged  and  prominent;  foot  drawn 
inward  and  upward,  broad  and  flat;  toes  short,  terminal  phalanges 
broad  and  square,  nails  flat  and  not  thickened. 

General  Musculature:  Muscles  large  and  soft,  small  amount  of 
adipose  tissue.  Face  had  a  peculiar  edematous  appearance.  Chest 
well  formed,  abdomen  distended  and  tympanitic.  Left  pleural  cavity 
contained  a  few  old  adhesions;  pericardium  negative.  Heart:  small 
amount  of  ante-mortem  clot  in  right  ventricle;  small  amount  of  sur- 
rounding fat;  muscle  solid  and  firm,  of  a  good  color;  normal;  weight 
15  ounces.  lyungs  slightly  congested;  bronchi  congested;  bronchial 
glands  slightly  enlarged,  otherwise  negative.  Much  gaseous  disten- 
tion of  intestines.  Acute  peritonitis,  slight  degree,  most  marked 
about  celiac  axis,  extending  over  toward  left  side.  In  the  region 
slightly  above  sigmoid  flexure  was  found  an  area  of  encysted  exu- 
date, not  purulent.  Spleen  was  adherent  to  cardiac  end  of  stomach 
and  elongated  to  a  length  of  6}^  inches;  weight  13  ounces.  Cap- 
sule rough,  covered  by  small  fibrous  masses,  granular  to  the  touch, 
light  in  color,  flabby  in  consistency,  not  congested.  Pancreas 
large,  tissue  very  light  in  color.  Stomach  distended;  large  amount 
of  acid-smelling,  dark,  undigested  food;  some  large  masses  of  cab- 
bage (?).  Stomach  wall  very  normal  in  appearance,  but  dilated. 
Caput  coli  very  much  dilated  with  fecal  matter;  appendix  long, 
adherent  to  posterior  surface  of  caecum;  no  intestinal  lesions. 
Bladder  normal  in  appearance,  contained  small  amount  of  urine. 


ACROMEGALY  69 

lyiver  large  and  light  in  color;  arteries  not  thickened;  substance 
friable  and  not  granular;  weight  8  pounds  i  ounce.  Gall-bladder 
distended,  duct  patulous.  Adrenals  normal  in  appearance;  right 
kidney  fatty  and  granular;  pelvis  of  left  kidney  dilated  and  dis- 
tended with  urine;  pyramids  of  both  kidneys  con  jested,  markings 
distinct;  capsules  slightly  adherent;  vessel  walls  normal;  pelvis 
dilated;  cortex  thin;  united  weight,  i>^  pounds.  Head:  scar  the 
size  of  a  silver  half  dollar,  one  and  one-half  inches  to  the  right  of 
the  median  line,  on  a  line  extending  from  mastoid  process  to  mas- 
toid process;  skull-cap  greatly  thickened,  cancellous  tissue  small  in 
amount;  acute  meningitis  with  effusion,  most  extensive  over  ante- 
rior lobes. 

Pituitary  Body:  Rising  from  the  pituitary  fossa  and  inclining 
toward  the  left  was  found  an  ovoid  red  mass,  measuring  1.5  centi- 
meters antero  -  posteriorly  and  .7  centimeter  vertically.  It  was 
attached  below,  apparently,  to  the  pituitary  body.  It  was  of  a 
soft  and  jelly-like  consistence  and  quite  vascular.  It  pressed 
directly  on  the  left  optic  tract,  just  posterior  to  the  chiasm.  The 
tumor  was  attached  to  the  hypophysis,  which  was  enlarged  to  about 
five  times  its  usual  volume.  The  pituitary  fossa  was  greatly 
enlarged  and  the  bones  comprising  its  wall  were  abnormally  thin. 
No  adhesions  existed  between  the  pituitary  body  or  tumor. 

SKKLKTON   OF  A   GIANT. 

Of  the  person  whose  skeleton  I  propose  to  describe,  nothing  is 
known,  with  the  exception  of  one  fact — that  he  was  a  native  of 
Kentucky,  U.  S.  A.  In  the  year  1877,  Prof.  Joseph  I^eidy  was 
informed  by  Prof.  A.  B.  Foote  that  a  body  of  a  giant  was  offered 
for  sale,  provided  no  questions  were  asked  which  might  lead  to  its 
identification.  Arrangements  were  soon  made  by  Dr.  William  Hunt 
through  the  gentlemen  mentioned  above,  and  the  body  was  trans- 
ferred to  Philadelphia,  where  the  skeleton  was  prepared  and 
mounted  by  Mr.  R.  H.   Nash. 

All  the  persons  mentioned  are  now  dead.  They  were  never  able 
to  ascertain,  or,  at  least,  thought  it  prudent  not  to  make  inquiry  as 
to  the  antecedents  of  this  giant,  whose  skeleton,  the  largest  and 
most  interesting  in  America,  now  adorns  the  Miitter  Museum  of 
the  College  of  Physicians  of  Philadelphia. 

It  will  be  interesting  to  make  a  comparison  of  this  skeleton,  as  a 
whole,  and  the  individual  bones  composing  it,  with  some  of  the 
famous  giants  of  which  we  have  records,  and  particularly  with 
skeletons  of  giants  in  lyondon  and  Dublin,  and  with  the  acro- 
megalic  skeleton  in  Edinburgh,  which  has  attracted  world-wide 


70 


ACROMEGALY 


Fig.  28.— Normal  skeleton.  Height,  6  feet  i 
inch.  (From  the  private  collection  of  Dr. 
George  McClellan.) 


Fig.  29.— The  American  giant. 
6  inches. 


Height,  7  feet 


ACROMEGALY  71 

attention.  The  author  is  indebted  to  Professor  Cunningham  for 
measurements  of  these  last  named  skeletons,  and  he  has  endeav- 
ored so  to  arrange  his  description  as  to  conform  to  the  model  which 
Professor  Cunningham  has  given.  Not  having  been  furnished  with 
any  name  for  the  person  whose  skeleton  I  describe,  I  shall  refer  to 
him  as  the  American  Giant. 

Height. — It  is  probable  that  the  American  Giant  had  attained 
the  age  of  22  or  24  at  the  time  of  his  death.  The  bones  seem  to 
have  attained  their  full  development,  although  the  epiphyseal  junc- 
tions are  plainly  visible  in  all  the  long  bones. 

The  spine  has  undergone  a  kyphoskoliosis  which  detracts  consid- 
erably from  the  height  which  would  otherwise  exist.  Taking  the 
skeletion  as  we  find  it,  the  height  is  seven  feet  six  inches.  This 
measurement  includes  suitable  artificial  intervertebral  disks,  which 
were  supplied  in  its  preparation.  There  is  a  rule  formulated  by  the 
late  Prof.  Sir  George  Humphrey^  by  which  we  may  consider  the 
height  of  any  individual,  under  normal  circumstances,  to  stand  in 
proportion  to  the  length  of  the  femur  as  1000  to  275.  But  in  our 
case,  as  in  other  abnormal  skeletons,  this  rule  may  lead  us  astray; 
whatever  the  error  may  be  in  short  skeletons  or  those  of  moderate 
height,  in  the  case  of  giants  the  disproportionate  length  of  the  long 
bones,  particularly  those  of  the  lower  extremity,  used  as  a  basis  of 
calculation,  will  lead  us  to  a  slightly  exaggerated  estimate  of  the 
total  height.  Applying  this  rule,  however,  to  the  American  Giant, 
we  have  R.  275:1000:  •.6^0:236^  —  L.  275:1000:  •.666:2421,  which 
equals  seven  feet  eight  and  three-quarter  inches  in  case  we  estimate 
by  the  right  femur,  and  seven  feet  and  eleven  inches  in  using  the 
left  femur. 

The  measurements,  therefore,  as  given  in  the  following  table 
taken  from  the  skeleton  itself,  doubtless  underestimate  the  size  of 
the  giant  in  life,  before  kyphosis  became  extreme. 

Mm.  Ft.  In. 

T.  An  Austrian,  de  TExpos.  Sc.  Anth.  de  Paris 2550  8  i^% 

R.  Marianne  Wehde 2550  8  45^ 

T.  A  Kalmuck,  Orfila  Museum 2530  8  35^ 

T.  A  Swedish  guard  of  Frederick  II 2520  8  3H 

R.  Chang 2360  7  8K 

C.  Byrne,  R.C.S.E 2310  7  7 

R.  Drasal  (Olmutz) 2300  7  6% 

A.  The  American  Giant 2295  7  6 

V.  Winkelmeier,  born  in  Upper  Austria 2278  7  5f^ 

R.  Thos.  Hasler,  Bavaria  (acromegalic?) 2270  7  s% 

A.  Henry  Alexander  Cooper  (Yorkshire  Giant) 7  5 

I,.  Innsbruck  Giant 2226  7  zVs 

V.  Murphy  (Irish),  Marseilles  Museum 2220  7  3% 

I,.  Berlin  (Cat.  No.  3040),  one  of  the  famous  guards  of  Frederick  II 2220  7  2% 

L.  Ivolly,  Pomeranian,  St.  Petersburg 2195  7  2% 

C.  Magrath  (Irish  Giant),  Dublin 2177  7  2"% 

T.,  Topinard;  C,  Cunningham;  I,.,  Langer;  R.,  Ranke;  V.,  Virchow;  A.,  Author. 

1  Human  Skeleton,  1858,  Table  IV,  page  108. 


72 


ACROMEGALY 


Fig.  30.— Americafl  giant;  posterior  aspect. 


Fig.  31. — American  giant;  side  view. 


ACROMEGALY 


73 


Bones. — The  Skull:  The  skull  of  the  American  Giant  bears  a 
fair  proportion  to  the  great  size  of  the  skeleton.  There  has  been 
some  discussion  among  craniologists  as  to  the  usual  ratio  of  the  size 
of  the  skull  to  that  of  the  skeleton  in  the  case  of  giants.  Virchow 
maintains  that  the  horizontal  circumference  and  the  various  diam- 
eters of  the  cranium  exceed  the  average.  He  states,  however,  that 
the  basis  cranii  is  relatively  short.  I^anger  holds  that  the  head  in 
giants  is,  as  a  rule,  relatively  small. 


Skull  measurement. 


Cubic  capacity,  Cc 

Length,  glabella-occipital 

internal 

Height,  basi-bregmatic 

binaural  over  bregma 

Vertical  index 

Breadth,  maximum 

minimum  frontal 

Cephalic  index 

Horizontal  circumference 

Length  of  foramen  magnum.... 
Breadth  of  foramen  magnum  .. 

Interzygomatic  breadth 

Intermalar  breadth 

Facial  index 

Orbital  width 

Orbital  height 

Orbital  index 

Palato-maxillary  length 

Palato-maxillary  breadth 

Palato-maxillary  index 


American 

Irish 

Byrne, 

Giant. 

Giant. 

R.  C.  S.  E. 

2320 

1600 

1520 

234 

198 

215 

195 

139 

148 

78.3 

70.2 

"68  8 

145 

155 

151 

640 

78.3 
568 

70.2 
593 

51 

40 

43 

39 
147 

■156 

148 

133 

■■'61.5 

55.4 

52 

44 

42 

42 
80 

43 
97-7 

34 
81 

50 
65 

61 
62 

130 

101.6 

Edinburgh  acro- 
megalic sk. 


1580 
200 


142 
71 


74 

561 

33 

150 
126 

54 
45 
36 


67 
70 
104.4 


The  measurements,  therefore,  show  that  we  have  to  do  with  a 
truly  gigantic  skull,  its  internal  capacity  being  nearly  one -half 
again  as  large  as  in  the  case  of  the  skeletons  in  London,  Dublin, 
and  Edinburgh.  The  increased  capacity  is  chiefly  due  to  increased 
length,  by  reason  of  which  the  skull  is  classed  as  dolicho-cephalic. 
The  interzygomatic  diameter  is  slightly  under  that  of  the  three 
skulls  with  which  we  have  compared  it.  The  intermalar  breadth, 
on  the  other  hand,  is  in  excess,  due  largely  to  the  great  develop- 
ment of  the  antrum.  The  frontal  sinuses  have  the  following  diam- 
eters: Transverse,  7.5;  vertical,  7;  antero-posterior,  supra-orbital, 
2.4. 


Pituitary  fossa. 


American 
Giant. 


Magrath. 


Edinburgh 
skeleton. 


Length. 
Depth.. 
Breadth 


22.5 
28 


Face. — The  face  is  large,  even  in  proportion  to  the  large  cranium. 
The  air  sinu.ses  are  large  and  give  the  great  intermalar  measure- 
ment, and  the  inferior  maxilla,  slightly  prognathous,  is  massive. 


74 


ACROMEGALY 


VERTICAL   DEPTH   OF   FACE    (NASION   TO   CHIN). 


I,ength  of  face.         Stature. 


Face-stature 
index. 


American  Giant 

Irish  Giant 

Winkelmeier 

Edinburgh  acromegalic 

Murphy 

Byrne,  R.  C.  S.  E 

Normal 


148 
156 
149 
148 
143 
137 
120 


2285 
2177 
2278 
1830 
2220 
2287 


Naso-alveolar 
length. 

Naso-alveolar 
stature  index. 

American  Giant 

90 
96 
82 
81 
73 

3-93 
4.40 
358 
4.42 
4.26 

Irish  Giant 

Byrne,  R.  C.  S.  E 

The  mandible  is  a  large  bone,  as  will  be  seen  from  the  follow- 
ing measurements:  Intercondyloid,  141;  intergonial,  113;  mento- 
alveolar,  40;  width  at  angle,  33;  width  of  ramus,  40;  angle  of  ramus, 
140°. 


Fig.  32  — Skull  of  the  American  Giant  compared  with  a  normal  skull. 


ACROMEGALY 


75 


Fig.  33. — Skull  of  the  Aniericau  Giant  compared  with  normal  skull;  side  view. 

The  coronoid  process  rises  higher  than  the  condyloid  process. 
The  lower  jaw  is  prognathous,  so  that  the  four  incisor  teeth  project 
slightly  in  advance  of  the  corresponding  teeth  above.  All  the  teeth 
in  both  jaws  are  in  place  and  nearly  all  are  incrusted  with  tartar. 


American  Giant . 

Irish  Giant 

Edinburgh  skull. 
Byrne,  R.  C.  S.  % 
Average 


I^ength  of    the    face 

from  nasion  to  chin 

Naso-alveolar  length 

compared  with  the 

compared  with  size 

size  of  the  cranium. 

of  the  cranium. 

Circumference,  100. 

circumference,  100. 

30  23.1 

14.0 

27.4 

16.8 

26.3 

14.4 

23-1 

13-8 

22.8 

13-8 

These  indices  show  that  there  is  a  slight  excess  in  both  the  max- 
illary and  mandibular  portions  of  the  face.  The  alveolar  portions  of 
the  jaw  are  perfect,  having- undergone  no  absorption. 

Relation  of  maxillary  to  mandibular  portions  of  the  face;  sym- 
physeal  height,  loo:  American  Giant,  44;  Irish  Giant,  47.9;  Byrne, 
R.  S.  C.  K.,  50;  Edinburgh  skull,  56.4. 

The  orbits  are  extremely  capacious. 

Vertebral  Column. — The  vertebrae  are  subject  to  conspicuous 
alteration,  but  they  have  been  so  mounted  as  to  give  a  correct 
representation  of  the  curves  which  existed  in  life.  As  usual  in 
acromegaly,  we  find  a  kyphoskoliosis,  in  which,  however,  the  cer- 
vical vertebrae  do  not  partake. 

Viewed  antero- posteriorly,  we  find  a  sharp  curve  in  the  dorsal 


76  ACROMEGALY  ^ 

and  lumbar  region,  with  the  convexity  to  the  right.  The  kyphosis 
reaches  its  maximum  at  the  ninth  thoracic  vertebra,  resulting  in  a 
compression  and  absorption  of  the  body  of  that  vertebra.  The 
following  are  the  measurements  of  the  anterior  surface  of  the 
vertebral  bodies:  Second  thoracic,  30  millimeters;  third  thoracic, 
28  millimeters;  seventh  thoracic,  25  millimeters;  ninth  thoracic,  10 
millimeters;  eleventh  thoracic,  31  millimeters;  first  lumbar,  36  mil- 
limeters; second  lumbar,  43  millimeters;  third  lumbar,  45  millime- 
ters; fourth  lumbar,  47  millimeters;  fifth  lumbar,  50  millimeters. 
Greatest  width  of  the  first  thoracic  vertebra,  97  millimeters  (3.75 
inches).  From  the  atlas  to  the  promontory  of  the  sacrum,  820 
millimeters;  from  the  same  points  in  a  direct  line,  750  millimeters; 
from  the  atlas  to  the  tip  of  the  cocc5^x,  along  the  anterior  borders 
of  the  vertebrae,  1030  millimeters. 

Viewed  laterally,  we  find  the  first  four  thoracic  vertebral  spines 
prominent  in  the  convexity;  next,  the  right  transverse  processes  of 
the  sixth,  seventh,  eighth,  ninth,  tenth  and  eleventh  vertebrae; 
then  the  spinous  processes  of  the  twelfth  thoracic  and  the  lumbar 
vertebrae.  The  great  lateral  displacement  of  the  vertebrae  brings 
the  posterior  margin  of  the  right  scapula  seven  centimeters  behind 
the  corresponding  margin  of  the  left,  and  in  line  with  the  right 
transverse  process  of  the  seventh  thoracic  vertebra. 

The  lumbar  vertebrae  are  massive.  The  sacrum  is  composed  of 
four  vertebrae,  instead  of  the  usual  number,  five.  Its  width  is  16 
centimeters;  length,  13.2. 

The  coccyx  consists  of  three  vertebrae,  instead  of  the  usual 
number,  four. 

The  ribs  are  long  and  narrow,  and  relatively  straight.  The 
seventh  and  eighth  right  ribs,  measured  along  the  under  border, 
are  45  centimeters  and  43.5  centimeters  in  length;  the  sixth  rib  on 
the  left  side  on  the  outer  side  is  43.5  centimeters  long;  the  seventh, 
measured  along  the  under  side,  is  43.8  centimeters  in  length. 

The  sternum  has  a  total  length  of  23.5  centimeters.  It  is  a 
large,  well-proportioned  bone. 


Manubrium 

Gladiolus,  ist  segment. 

remainder.... 

Ensiform  cartilage 


Ivcngth. 


6.7  cm. 

4 

8.9 


Width. 


8.4 

4 

5-S 


The  thorax  is  large,  but  narrow  in  proportion  to  its  depth. 
Girth,  109.7  centimeters  (43^  inches);  antero-posterior  diameter, 
43  centimeters;  lateral  diameter,  28  centimeters. 


ACROMEGALY  77 

This  corresponds  with  Langer's  observation  that  in  individuals 
of  great  stature  the  thorax  is  relatively  narrow.  In  this  respect  the 
American  Giant  differs  from  the  Irish  Giant,  Magrath,  whose  broad 
chest  and  boldly  curved  ribs  give  a  girth  of  132  centimeters  (52^ 
inches). 

Pelvis. — The  pelvis  is  large  and  proportionate  to  the  size  of 
the  skeleton.  The  bones  are  thickened  at  their  borders  and  bear 
the  marks  of  periosteal  inflammation.  Especially  is  this  noticeable 
in  the  iliac  crests  and  above  the  acetabula,  which  are  evidently 
arthritic.  The  conformation  is  of  the  rachitic  type,  judging  from 
the  increase  of  the  measurement  between  the  anterior  superior  spines 
and  the  crests. 

Centimeters. 

Between  the  anterior  superior  spines 35.5 

Between  the  crests 33,5 

Between  the  middle  points  of  the  ischii 15.5 

Antero-posterior  diameter  of  the  pelvic  inlet 14. 

Right  anterior  oblique  diameter  of  the  pelvic  inlet 17.5 

I^eft  anterior  oblique  diameter  of  the  pelvic  inlet 17.7 

Depth  of  pelvic  cavity 

Height  of  pelvis 

This  pelvis  is  thus  somewhat  smaller  than  that  of  Magrath 
(Dublin)  and  of  Byrne  (R.C.S.E.).  The  latter  have  a  breadth  of 
38.6  and  38  centimeters  respectively. 

The  cavity  of  the  pelvis  is  considerably  encroached  upon  by  the 
convexities  which  mark  the  position  of  the  acetabula,  particularly 
that  of  the  left  side.  The  acetabula  are  very  deep  and  separated  by 
thin  bone  from  the  pelvic  cavity.  The  bodies  of  the  iliac  bones  are 
exceedingly  thin. 

Upper  Extremity. — The  clavicles:  Length,  212  millimeters.  The 
scapulae:  Length,  acromion  to  angle,  R.  268,  L-  268  millimeters; 
breadth,  R.  144,  L.  150. 

The  Humeri. — The  right  humerus  is  47.5  centimeters  long  and 
has  a  circular  perforation  in  the  olecranon  fossa  16  millimeters  in 
diameter. 


I<ength  of  humerus. 


Right. 


Iveft. 


Relation  of  humerus 

to  stature. 

(Stature  =  loo. ) 


Right. 


Left. 


American  Giant 

Irish   Giant 

Byrne 

Edinburgh  skeleton 

Average,  98.8,  Topinard. 


47-5 
43-1 
45-0 
34-8 


43-3 
43 -o 
33-1 


19.7 
19.0 
19.6 


19.8 
18. 1 


78 


ACROMEGALY 


Ulna. — Right  ulna  37.8,  left  ulua  37.5  centimeters  long. 
Radius. — Right,  354;  left,  360. 

Hand. — IvCngth  of  hand  from  scaphoid  to  tip  of  middle  finger  is 
25  centimeters. 


I,engtli  of  hand. 

Relation  to  stature. 
(Stature  =  loo.) 

American  Giant 

25.0  centimeters. 
25.8  centimeters. 
26.3  centimeters. 

10.9 
II. 8 

Byrne  (R.  C.  S.  E.) 

II-3 

Lower  Extremity. — Femora:  The  femora,  though  slender,  in 
proportion  to  the  great  size  of  the  body,  are  symmetrical,  and 
the  shafts  are  well  formed  and  not  unduly  curved.  They  vary 
II  millimeters  in  length;  the  right  is  65.5  centimeters  in  length; 
the  left,  66.6.  The  shafts  are  84  and  85  millimeters  in  circumfer- 
ence for  the  right  and  left  sides  respectively,  and  20  millimeters  in 
diameter.  The  shafts  are  thus  no  thicker  than  in  ordinary  indi- 
viduals. The  hip- joints  are  markedly  arthritic.  The  femoral  heads 
are  misshapen  and  the  necks  are  deformed.  The  latter,  instead  of 
being  circular  in  shape  on  cross-section,  are  semilunar,  with  the  flat 
side  anterior;  they  are  short  and,  instead  of  being  placed  obliquely, 
approach  a  right  angle  in  relation  to  the  shaft.  The  circumference 
and  greatest  diameter  of  the  necks  are  as  follows:  Circumference, 
right,  13.5;  left,  13.     Greatest  diameter,  right,  5.7;  left,  5.5. 

The  condyles  are  well  formed  and  bear  a  proper  relation  to  the 
tibiae.  The  compact  tissue  is  very  thin  at  the  extremities,  barely 
covering  the  cancellous  structure. 


American  Giant 

Irish  Giant  (Magrath) 

Byrne,  R.C.S.E 

Edinburgh  skeleton 


TibicB  and  Fibulae. — The  fibulae  curve  with  their  convexity  back- 
ward, so  that  the  perpendicular  to  the  chord  of  the  arc  is  47  milli- 
meters. The  middle  portion  of  the  shaft  in  both  cases  lies  entirely 
posterior  to  the  tibiae. 


ACROMEGALY 


79 


American  Giant 

Irish  Giant  (Magrath) 

Byrne,  R.C.S.E 

Edinburgh  skeleton.... 


I^ength  of  tibia. 


Right. 


55-5 
50.6 
54-1 
40.2 


Left. 


56.5 
50-4 
53-7 
39-2 


Relation  of  tibia  to 

stature. 

(Stature  =  100.) 


Right. 


24-3 
23.2 
23.6 
21.9 


Left. 


24.7 
23.1 
23-4 
21.4 


THE  FOOT. 


American  Giant 

Irish  Giant  (Magrath) 

Byrne,  R  C.S  E 

Murphyi 

Winkelmeieri  

J.  W.  Walker's  casei  . 


Actual  length. 


306 
300 

317 
310 
358 
360 


"•75 
12.50 
12.25 
14.12 
14-13 


Compared  with 

skeleton. 
(Stature  =  100.) 


1  Measured  during  life. 


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Campbell,  E.  K. :  Tr.  Clinical  Soc.  of  London,  April  24,  1896;  British  Medical  Journal, 

1896,  i,  p.  1091;  British  Medical  Journal,  1895,  i,  p.  81;  Tr.  Clinical  Soc.  of  Lond.,  1890,  xxiii,  p. 
257,  and  1894. 

Carpenter,  H.  ^ .:  Journal  of  the  American  Medical  Association,  1897,  i,  p.  1043. 
Carr-White:  Edinburgh  Medical  Journal,  1889. 

Caton,  R.:  "Treated  by  Operation,"  British  Medical  Journal,  Dec.  30,  1893,  p.  1421;  Liver- 
pool Medico-Chiriirgical  Journal,  1893,  369. 

Caton,  R.,  and  Paul,  F.  T.:  "Acromegaly  Treated  by  Operation,"  British  Medical  Journal, 

1893,  ii,  1421. 

Cattell,  H.  W.:  "Skiagraph  of  an  Acromegalic  Hand,"  International  Clinics,  July,  1896. 

Cenas:  "Supposed  Congenital  Case,"  Im.  Loire  Medicate,  Dec.  15,  1890. 

Cepeda,  G.:  Rev.  Balear  de  Cienc.  Med.,  Palma  de  Mallorca,  1892,  viii,  7. 

Chadbourne,  T.  L.:  "A  Case  of  Acromegaly  with  Diabetes,"  N.  Y.  Med.  Jour.,  April  2,  1898. 

Chalk:  Trans.  Path.  Soc.  of  London,  1857,  vol.  viii,  p.  305. 

Chantemesse,  M.:  "  Sur  un  cas  de  Syringomyelic  a  forme  Acromegalique,"  Le  Progrls 
Med.,  1891,  i,  p.  273. 

Chappell,  W.  F.:  "Larynx  in  Acromegaly,"  A?ner.  Med.  Surg.  Bulletin,  Jan.  iS,  1896; 
AUbutt's  System  of  Medicine,  vol.  v,  p.  806. 

Chauffard,  A.:  Abeille  Med.,  1895,  Hi,  244;  Bull,  et  Mem.  Soc.  Med.  de  Hop.,  1895,  35,  xii,  542; 
"Acromegalic  fruste  avec  macroglossie,"  La  Semaine  Medicate,  1895,  p.  305. 

Chealde  et  Lannois:  De  la  cachexie  pachydermique. 

Charon,  P.:  V Union  Medicate,  Jan.  6,  8,  1891. 


ACROMEGALY  8i 

Church,  A.,  and  Hessert,  W.:  Medical  Record,  1893,  xliii,  p.  545. 
Clair-Sy  miners:  British  Medical  Journal,  1891. 

Claus,  A.:  A^in.  Soc.  de  Med.  de  Gaud,  1890,  vol.  Ixix;  and  1893,  vol.  Ixxii. 
Claus,  A.,  and  Van  der  Stricht,  O.:  Ibid.,  1893,  p.  71. 

Cohen,  S.  S.:  Tr.  Coll.  Phys.  Phila.,  1892;  Medical  News,  1892,  p.  518;  Alienist  and  Neu- 
rologist, 1894,  374;  College  and  Clinical  Record,  1894,  112;  Interuatiotial  Clinics,  1894,  ii,  57. 

Collins,  J.:  Journal  of  Nervous  and  Me^ital  Disease,  1893,  xx,  pp.  48-129,  and  p.  917. 

Comini,  E.:  Arch ivio per  de  Sc.  Med.,  vol.  xx,  Fasc.  iv,  1896. 

Costanzo,  Feliciano:  Rivista  Veneta  di  Scienze  Medtche,yx.\\,\'^'^,  Venezia;  Centralb.  f. 
Nervenheilkunde,  xviii,  1895,  p.  459. 

Crego,  F.  S.:  Medical  Record,  1894,  vol.  xlv,  p.  215. 

Crowell,  G.:  Trans.  Ophth.  Soc.  United  Kingdom,  I^ond.,  1890-91,  xi,  84-86. 

Cr6tien:  Rev.  de  Med.,  1893. 

Cunningham,  D.  J.:  The  Irish  Giant  (Acromegalic),  Trans.  Royal  Irish  Academy,  vol. 
xxix,  part  xvi,  1891. 

C.ur).u\n^\\2>.ra.-'t\\ovcisoxi.-.  Joiirnal  of  Anatomy  a7id  Physiology,  1889-90,  vol.  xxiv,  p.  475. 

Dallemagne:  Arch,  de  Mid.  Exper.  et  d^Anat.  Path.,  1895,  vii,  589.  Three  cases  with 
autopsy. 

Dalton,  N.:  "Acromegaly  and  Myxcedema,"  Lancet,  1897,  ii,  1190;  Trans.  Pathol.  Soc, 
I/Ond.,  1897. 

Dana,  C.  'L,.:  Journal  of  Nervous  and  Mental  Disease,  1893,  xx,  725,  and  1894,  p.  141. 

Day,  F.  I,.:  Trans.  Rhode  Island  Med.  Soc,  1889-93,  iv,  541;  Boston  Medical  and  Surgical 
Journal,  1893,  p.  725. 

Debierre:  Rev.  Gen.  d'Ophtal,  Paris,  1891,  x,  12. 

Denti:  Atti  di  Assoc.  Med.  I^omb.  Milano,  1892,  41;  Annali  d'Ottalm.,  xxv,  1896,  Fasc.  6. 

Dercum,  F.  X.:  Ajnerican  Journal  of  the  Medical  Sciences,  Philadelphia,  1893,  cv,  268. 

D'Fsterre,  John  Norcott:  "Case  of  Acromegaly,"  British  Medical  Journal,  Dec.  4,  1897. 

Dethlefsen:  Med.  Aarsskv.  Kjobeti,  1892,  83-88. 

Dinke:  (See  Vinke). 

Dodgson,  R.  W.:  Lancet,  1896,  i,  772;  British  Medical  Journal,  March  14,  1896. 

Daebbelin,  C:  "  Pseudo-acromegalie  and  Acromegalic,"  Thesis  Konigsberg,  1S95. 

Doyne:  "Optic  Atrophy  in  Acromegaly,  with  Charts  of  Fields  of  Vision,"  Trans. 
Ophthal.  Soc.  United  Kingdom,  1895. 

Dreschfeld,  J.:  British  Medical  Journal,  Jan.  6,  1894,  p.  4. 

Du  Cazal:  Bull,  et  Mem.  Soc.  Med.  d.  Hop.  de  Paris,  1891,  viii,  485;  P>-ogrls  Medical,  1891, 
ii,  pp.  295  and  585;  La  Semaine  Medicate,  Paris,  Oct.  2i,  1891. 

Duchesneau,  G.:  Paris,  1892,  De  I,' Acromegalia. 

Dulles,  C.  W. :  Medical  News,  1892,  No.  5. 

Dyson,  W. :  Quarterly  Medical  Journal,  '^a^nua.ry,  1894. 

Editorial,  Medical  News,  April  9,  1892. 

EJllinwood:  San  Francisco  Laiicet,  1883,  p.  159. 

Elliott:  Lancet,  1888. 

Erb:  "Ueber  Krankhaften  Riesenwuchs,"  Deutsches  Archiv  f.  Klin.  Med.,  1888,  Bd.  42; 
Naturforscherversamm.lung  in  Heidelberg,  September,  1889,  No.  62;  Miinchener  3Ied.  IVoch., 
1894,  No.  24. 

Eschle:   Therap.  Monats.,  January,  1896. 

Eshner,  A.  A. :  Medical  News,  1895,  Ixvii,  458. 

Ewald:  Bert.  Klin.  IVoch.,  March  18,  1888;   Virchow's  Archiv,  Bd.  Ivi,  1892. 

Farge:  Prog.  Med.,  1889,  2d  series,  x,  July  6. 

Fazio,  F. ;  La  Riforma  Med.,  1896,  ii,  p.  399. 

Feld,  F.  A.:  Case  showing  acromegaly  and  hypertrophic  pulmonary  arthropathy, 
British  Medical  Journal,  July  i,  1893,  p.  14. 

Finlayson,  James:  International  Clinics,  October,  1896. 

Flemming,  Percy:  Trans.  Clinical  Soc.  of  I,ondon,  1890. 

Fournier,  J.  B.  C:  "Acrotnegalie  et  troubles  cardio-vasculaires,"  T/i^se  de  Paris,  1S96. 

Foy,  G.:  "  Cheiromegaly,"  Medical  Press  and  Circular,  1891,  lii,  491. 

Fraenkel,  A.:  Munchener  Med.  IVoch.,  1897,  P-  40i. 

Fraentzel,  O.:  Deutsche  Med.  Woch.,  1888,  xiv,  651. 

Franke:  Case  with  temporal  hemianopsia,  Klin.  Monatsbl.f.  Augenh.,  1896,  p.  259. 

Fratnich,  E.:  Allgemeine  Wiener-  Med.  Zeitung,  1893,  No.  40,  and  1892,  No.  37;  Riv.  Veneta 
di  Sc.  Med.,  Venezia,  1892,  xvii,  238. 

Freund,  W.  A.:  Sa7n7nl.  Klin.  Vort.,  1889,  Nos.  329  and  330;  Rev.  de  Sciences  Medicates, 
xxxiv,  p.  569. 

Friedreich:    Virchow^s  Archiv,   Bd.  xlvii,  i858,  83.     Hyperostosis,  etc. 


82  ACROMEGALY  ^ 

Kritsche  und  Klebs:  Ein  Beitrag  zur  Pathologic  des  Riesenwuchses,  Leipzig,  1884. 
Furnivall,  Percy:  Lancet,  ii,  1897,  p.  1190. 

Gajkiewicz,  W.:  Gaz.  lek.  JVat-sawa,  1891,  Nos.  43  and  44,  25,  xi,  and  1896,  No.  37;  "  Pseudo- 
akromegalie  und  Akromegalie,"  Inaug.  Dissert.,  Konigsberg,  1895. 

Galvani:  J?ev.  d'Orthop.,  Paris,  1895,  vi. 

Garaud  et  Arene:  Loire  Med.  St.  Etienne,  1895,  xiv. 

Gaston  et  Brouardel:  "  Rontgen  Photography  in  Acromegaly,"  La  Presse  Med.,  1896,  No.  61. 
Gause:  Deutsche  Med.  IVoch.,  1892,  xviii,  891. 

Gauthier,  G.:  Prog.  Med.,  1890,  2  S.,  xi,  409-414,  and  1892,  No.  i. 

Gerhardt:  Bet-liner  Klin.  Woch.,  Dec.  15,  1890. 

Gessler,  H.:  Med.  Corresp.-Bl.  d.  Wurtemb.  arzt.,  Stuttgart,  1893,  Ixiii,  121. 

Gley,  E.:   "  Recherches  sur  la  fonction  de  la  glande  thyroide,"  Bull,  de  la  Soc.  de  Biol., 
April  18,  1891;  Arch,  de  Physiol.  Norm,  et  Path.,  1892,  pp.  81,  311,  435. 

Godlee,  R.  J.:  Trans.  Clin.  Soc.  Lond.,  1888,  and  British  Medical  Journal,  1888. 

Goldsmith,  C.  P.:  Lancet,  1896,  i,  993. 

Gonzalez  Cepeda,  J.:  Rev.  balear  de  Cien.  Med.,  Palma  de  Mallorca,  1892,  viii. 

Gordon-Brown:  British  Medical  Journal,  April  23,  1892. 

Gardinier,  H.  C. :  Medical  News,  1895,  Ixvii,  262. 

Gouraud,  X.:  Bull,  de  la  Soc.  Med.  des  Hbp.,  1889. 

Gubian:  Bull.  d.  Dispe?isaire  de  Lyon,  1811. 

Gorjatscheflf:  Chir.  Lepopisj.,  Bd.  i,  1892.     Moskau. 

Graham,  J.  B-:  Trans.  Ass.  Amer.  Phys.,  1890,  v;  Medical  News,  Oct.  18,  1890. 

Grasset  et  Rauzier:  Maladies  du  Systeme  Nerveux,  4th  Ed.,  1894,  ii. 

Grifi&th,  Alex.  Hill:  Case  of  sarcoma  of  hypophysis,  British  Medical  Journal,  1895,  ii,  950. 

Grocco:  Rev.  gen.  Ital.,  Pisa,  1891. 

Gr6n,  Kr.:  "  Hypertrophy  of  the  Hypophysis  in  a  Case  of  Myxcedema,"  Norsk  Magazin 
for  LcEgevidenskaben,  1894,  P-  734- 

Gubian:  Bull,  de  Dispensaire  de  Lyon,  1891,  No.  16. 

Guinon  and  Surmont:  Nouvelle  Lconogr.  de  la  SalpHrilre,  tome  iii,  Paris,  1890,  pp.  147-160. 

Guinon,  G.:  Gaz.  d.  Hop.,  Paris,  1889,  Ixii,  1161. 

Gulliver:  Tr.  Path.  Soc.  Lond.,  vol.  xxxvii,  p.  511. 

Hadden  and  Ballance:  Trans.  Clin.  Soc.  Lond.,  1888,  xxi,  and  1885,  xviii. 

Haller:  "Morphology  of  the  Hypophysis  Cerebri,"  Morphol.  Jahrbuch,  xxv,  1896. 

Hanseman,  D.:  "  tjber  Akromegalie,"  Deutsche  Medizinal-Zeitung,  Feb.  4,  1897;  Berliner 
Klin.  Woch.,  1897,  No.  20. 

Hare,  H.  ^.■.  Journal  of  Nervous  and  Mental  Disease,  1892,  250;  Medical  News,  1892,  257. 

Harris,  H.  F. :  Medical  News,  Ixi,  520. 

Hascovec,  L.:  Rev.  de  Med.,  March  10,  1893,  p.  237;  Wiener  Klin.  Rund.,  April  28,  1895. 

Higier:   Tageblatt  der  Versa^nmlungen  Deutscher  Naturforscher,  etc.,  Wien,  1894,  p.  309. 

Hinsdale,  Guy:  Medicine,  June,  July,  August,  September,  and  October,  1898. 

Henrot,  H.:  Notes  de  Clinique  Med.,  Rheims,  1882  and  1887. 

Hitschmann,  R.:  "Acromegalic  und  Augenbefunde,"  Wiener  Med.  Club,  June  16,  1897; 
Wiener  Klin.  Woch.,  1897,  p.  659. 

Hertel,  E.:  Arch.fiir  Ophthal.,  1895,  xli,  i. 

Herzog,  B.:  Deutsche  Med.  Woch.,  1894,  316. 

Hofmeister:  "Experimental  Research  on  Ablation  of  the  Thyroid,"  Fortschr.  d.  Med., 
1892,  p.  81. 

HolschewnikofF:  "Acromegaly  and  Syringomyelia,"  Virchow's  Archiv,  vol.  cxix,  p.  10. 

Holsti:  Festskrwd  /ran  Pathologisk-Atiatotnisk  Institut.,  Helsingfors,  1890;  Zeitschr.  fiXr 
Klin.  Med.,  Bd.  xx. 

Hornstein:   Virchow's  Archiv,  Bd.  xxxiii,  1893. 

Horsley,  V.:  "On  the  Functions  of  the  Thyroid,"  British  Medical  Journal,  1890,  ii,  201, 
and  1892,  i,  431. 

Howell,  W.  'B..:  Journal  of  Experimental  Medicine,  vol.  iii,  No.  2,  1898. 

Huchard,  H.:  "  Anat.  Path.,  lesions  et  troubles  cardio -  vasculaire  de  1' Acromegalic," 
Journal  des  Praticiens,  1895,  ii,  249. 

Hutchings,  R.  H.:  "Acromegaly  and  Mental  Disease,"  Medical  Standard,  Chicago,  1895, 
xvii,  129. 

Hutchinson,  Woods:  "Acromegaly  in  a  Giantess,"  American  Journal  of  the  Medical  Sci- 
ences, 1895,  ex;  "  Function  of  the  Pituitary  Body,"  Medical  News,  1896,  ii,  p.  707;  "  The  Pituitary 
Gland  as  a  Factor  in  Acromegaly  and  Giantism,"  New  York  Medical  Journal,  March  12,  April 
2,  1898,  et  seq. 

Hutchinson,  J.:  Three  cases,  Archives  of  Surgery,  London,  April,  1891,  and  1889-90,  i,  pp. 
141-148. 


ACROMEGALY  83 

Jores:  (Bonn.) 

Jorge,  R.:  Arch,  de psichiat.,  Turin,  1894,  xx,  412. 

Kalindero:  La  Roumanie  MMicale,  1894,  p.  65. 

Kanthack:  British  Medical  Journal,  July  25,  1891. 

Karg:  Archivf.  Klin.  Chirurg.,  Bd.  xli,  p.  loi. 

Keen,  W.  W. :  "Kxcision  of  Nerves  in  Acromegaly,"  International  Clinics,  Philadelphia, 
1893.  3  S.,  ii,  191. 

Kerr:  Lancet,  1893,  ii,  1256. 

Koscheeff,  J.:  Protok.  Zasaid.  Obsh.  Vrach.  Viatke,  1892,  13-16. 

Kerner:   Vereinsblatt  der  Pfalzischen  Aerzte,  Frankenthal,  August,  1890. 

Kinnicutt,  F.  P.:  "Therapeutics  of  the  Internal  Secretions,"  A tnerican  Journal  of  the 
Medical  Sciences,  July,  1897. 

Klebs:  Allgem.  Path.,  1889,  ii. 

Klebs  und  Fritsche:  (Gigantism),  Ein  Beitrag  ztir  Pathologie  des  Rieseiiwuchses,  Leipzig, 
Vogel,  1884. 

Kojevnikoff,  A.  G.:  Med.  Obozr.  Moscau.,  1893. 

lyancereaux:  "Acromegalic  Trophoneuroses  of  the  Extremities;  its  Coexistence  with 
Exophthalmic  Goitre  and  Glycosuria,"  Medical  Week,  Paris,  1895,  iii,  109;  Anatomic  Patho- 
logique,  t.  iii,  i  re  Partie,  29. 

Lathuraz:  "Result  of  the  Autopsy  in  Pechadre's  Case,"  Lyon  Medicate,  1893,  vol.  Ixxiii, 

P-443- 

I,avielle,  C:  Mem.  et.  Bull.  Soc.  de  Med.  et  Chir.  de  Bordeaux,  1895,  xxiv,  i. 

Levi:  Archives  Gin.  de  Med.,  1896,  ii,  p.  579. 

lyichtheim:  Deutsche  Med.  JVoch.,  1893. 

Linsmayer,  I,:   Wiener  Kliyi.  Woch.,  1894,  vii,  294. 

Litthauer,  Max:  Deutsche  Med.  Woch.,  1891,  xvii,  1282. 

lyittle:  British  Medical  Journal,  1895,  ii,  p.  950. 

Lombroso:  "  Caso  Singolare  de  Macrosomia,"  Virchow''s  Archiv,  Bd.  xlvi,  1869,  253,  and 
Bd.  Ivi,  1872;  also  originally,  Giornale  Ital.  delle  Malattie  Ven.,  1868. 

Long:  Lehigh  Valley  Medical  Magazine,  April,  1891,  U.  S.  A. 

Lovegrace:  Lancet,  1892,  i,  p.  91. 

Luzet,  C:  Arch.  Gen.  de  Med.,  1891,  i,  194. 

Machado,  V.:  "  Semeiologia  Radiographique  de  1' Acromegalia,"  Revista  Portugzieza  de 
Med.  e  Cirurg.,  t.  iii.  No.  30,  Jan.  15,  1898. 

Mackie-Whyte:  Lancet,  1893,  i,  12. 

Magnus-Levy:  Munchener  Med.  Woch.,  1897,  p.  400. 

Macroq:  British  Medical  Journal,  1892. 

Mairet  and  Bosc:  Arch,  de  Phys.  Norm,  et  Path.,  1896,  vol.  viii,  p.  600. 

Marie,  P.,  and  Souza-Leite:  "  Essays  on  Acromegaly;  with  Bibliography,"  London, 1891. 

Marie  et  Marinesco:  Archives  de  Med.  Experiment  et  d'Anat.  Path.,  1891,  p.  539. 

Marie,  P.:  Rev.  de  Med.,  Paris,  1886,  vi,  297-333;  N.  Iconogr.  de  la  Salpitrih^e,  1888,  i,  173, 
and  1889,  ii,  45,  96,  139,  188,  224,  327;  Progris  Med.,  1889,  2  s.,  ix,  iii,  1579;  Lecons  de  Clinique  Med- 
icate, Paris,  1896,  p.  51;  Bull.  Med.,  1889,  iii,  1579;  Brain,  Lond.,  1889,  xii,  59;  Bull,  et  Mem.  de  la 
Soc.  des  Hdp.,  May  i,  1896  (Hands  in  Acrom.). 

Marina:  Riforma  Med.,  1893,  ix,  "Hypertrophic  Osteo-arthopathy  and  Acromegaly." 

Marinesco,  G.:  "Rontgen  Rays  in  Acromegaly,"  Comptes  rendus  Hebdoin.  des  Seances 
Societe  de  Biologie,  June,  19,  1896,  p.-  615;  ibid.,  1892,  p.  509;  Arch,  de  Mid.  Expir.  et  d'Anat. 
Path.,  1891,  iii,  539;  "Trois  Cas  d'acromegalie  traites  par  des  tablettes  de  corps  pituitaire," 
Bull,  el  Mim.  Soc.  Mid.  des  Hop.,  1895,  35,  xii,  715;  Verhandl.  d.  Internal.  Med.  Congr.,  1890, 
Berlin,  1891,  iv;  Semaine  Med.,  Nov.  13,  1895. 

Marino:  Berlifier  Klin.  Woch.,  1894,  p.  988. 

Marzocchi  et  Antonini:  "  Un  cas  d'acromegalie  partielle,"  Riforma  Med.,  January  22, 
1897,  No.  17. 

Masoin,  E:  "Apergus  genSrales  sur  la  phj'siologie  du  corps  thyroide,"  Revue  de  ques- 
tions Scientif,  April,  1894. 

Massalongo,  R.:  Rev.  Neurologique,  Paris,  1S95;  Riforma  Med.,  Napoli,  1892,  viii,  p.  10,  iii, 
74,  87;  "  Hyperfunction  der  Hypophyse,  Reisenwuchs  und  Acromegalic,"  Centra Ibl.  f.  Ner- 
venheilk.,  June,  1895. 

Mans,  J.:  "  Glandula  thyreoidea  und  Hypophysis  cerebri  mit  Hinweis  auf  die  niit 
demselben  in  Beziehung  stebenden  Krankheitserscheinungen,"  Dissert.,  Griefswald,  1895. 

Matignon,  J.  J.:  "  Un  cas  d'acromegalo-gigantisme  chez  uu  Chinois,"  La  Midecine 
Moderns,  1897,  No.  89. 

Medical  News,  1892,  Ix,  237. 

Mendel,  E.:  Berl.  Klin.  Woch.,  1895,  No.  48,  11 29. 


84  ACROMEGALY  ^ 

Mevel,  P.:  "Contribution  a  T^tude  des  troubles  Oculaire  dans  Acromegalie,"  Paris, 
1894.     Thesis. 

Meyer,  F.:  Ein  Fall  von  Akromegalie,  Hamburg,  1894.     Kieler  Dissert. 

Meyer  (Paris):  "  Ocular  Symptoms  in  Three  Cases  of  Acromegaly,"  British  Medical  Jour- 
nal, 1895,  ii,  949. 

Michel,  Middleton:  "  Pathology  of  the  Pituitary  Body,"  Charleston  Medical  Journal  and 
Review,  S.  G.,  vol.  xv,  March,  i860. 

Middleton,  G.  S.:  "A  Marked  Case  of  Acromegaly  with  Joint  AfTections,"  Glasgow 
Medical  Journal,  1894,  xli,  401;  ibid.,  1895,  xliv,  127. 

Minkowski,  O:  Berliner  Klin.  Woch.,  1887,  xxiv,  371,  and  xxi. 

Mistre,  A.:  Rev.  de  Cien.  Med.  Habana,  1895,  x,  209-216. 

Moebius:  SchniidV s  Jahrbiicher,  1892,  p.  22. 

Moncorvo:  "  Microcephalic  Case,"  Rev.  Mens.  d.  Mai.  de  VEnfan.,  Paris,  1892,  x,  549. 

Monteverdi  et  Torrachi:  "  Un  caso  di  acromegalia  con  emianopsia  bitemporale," 
Rivista  Sperimentale,  1897,  Reggio. 

Morax:  Neurolog.  Central  Organ.,  1892. 

Moritz:  Tageblatt  der  Versammlung  Deutscher  Naturforscher ,  Wien,  1894,  p.  309. 

Mosler,  C.  F.:  "  Pachy aerie,"  Festschrift  R.  Virchow,  Berl.,  1891,  ii,  loi;  IVien.  Med.  Bl., 
1892,  XV,  56,  70,  87,  105,  121,  136;  SchmidV s  Jahrbucher ,  1893,  No.  12,  p.  237. 

Moss6,  A.:  Comptes  Rend.  Sac.  de  Biol.,  Paris,  1895,  ii,  686;  La  Semaine  Medicate,  1895,  p. 
468;  Mercredi  Med.,  Sept.  11,  1895. 

Motais:  Prog.  Mid.,  1891,  May  7;  Annates  d'' Oculistique,  Jan. -Feb.,  1886,  p.  47. 

Moyer,  Harold  N.:  International  Medical  Magazine,  1894-5,  iii,  34. 

Murray,  F.  W.:  Annals  of  Surgery,  Philadelphia,  1893,  xvii,  700. 

Murray,  G.  R.:  "Clinical  Remarks  on  Cases  of  Acromegaly  and  Osteo-arthropathy," 
British  Medical  Journal,  1895,  i,  293;  "Acromegaly  with  Exophthalmic  Goitre,"  Edinburgh 
Medical  Journal,  February,  1897. 

O'Connor,  J.  T.:  N .  Amer .  Jour'.  Homeop.,  N.  Y.,  1888,  iii,  345. 

Naunyn:   Verei^isbeilage  der  Deutschen  Med.  Woch.,  1896,  p.  87. 

Nonne:   Vereinsbeilage  der  Deutschen  Med.  Woch.,  1896,  p.  14. 

Ogata,  K.:  Chiugai  Iji  Shinpo,  tokio,  1893,314. 

Olechnowicz,  W.:  Gaz.  lek.  Warszawa,  1894,  xiv,  113. 

Orsi,  F.:  Gazz.  Med.  Lonib.,  Milano,  1892,  Ii,  201. 

Orbillard:  Rev.  de  Med.,  1892. 

Orchiuzzi,  L.:  Incurabili,  Napoli,  1892,  vii,  350,  522,  549. 

Osier,  W.:  Principles  and  Practice  of  Medicine,  1895,  p.  1047. 

Osborne,  O.  T.:  American  Jour7ial  of  Medical  Sciences,  1892,  p.  617;  Yale  Medical  Journal, 
December,  1897;  Trans.  Association  Amer.  Phys.,  1897;  Buck's  Reference  Handbook  of  the 
Medical  Sciences,  Supplement,  1893. 

Ott,  Isaac:  "Note  on  Animal  Extracts,"  Medical  Bulletin,  Philadelphia,  1896,  p.  371. 

Packard,  F.  A.:  Trans.  Coll.  Phys.  Phila.,  1892;  American  Journal  of  the  Medical  Sciences, 

1892,  ciii,  657. 

Paget:  Lancet,  Jan.  31,  1891. 

Panas:  British  Medical  Journal,  1895,  ii,  p.  950. 

Parinaud:  Soc.  Francaise  d'Ophtahnologie,  Seance  du  2  Febrier,  1891. 

Park,  R.:  Internatio7ial  Medical  Magazine,  Philadelphia,  1895-6,  iv,  431. 

Parsons,  R.  'L,.:  Journal  of  Nervous  and  Mental  Disease,  1894,  xxi,  717;  New  Yoj'k  Medical 
Journal,  1894,  lix,  88. 

Pechadre:  Rev.  de  Med.,  1890,  x,  175;  Lyon  Med.,  1893,  vol.  Ixxiii,  p.  443. 

Pel:  Berliner  Klin.  Woch.,  No.  3,  1891. 

Pershing,  H.  T.:  Journal  of  Nervous  and  Mental  Disease,  1894,  xxi,  693;  International 
Medical  Magazine,  1894-5,  iii,  327. 

Peterson,  Frederick:   "Acromegaly  Combined  with  Syringomyelia,"   Medical  Record, 

1893,  xliv,  391. 

Pfliiger:  Rev.  Gtn.  d'Ophthal.,  1892,  7. 

Phillips,  S.:  Trans.  Med.  Soc.  Lond.,  1891-2,  xv,  455;  British  Medical  Journal,  Feb.  27,  1892. 

Pick,  A.:  Prag.  Med.  Wodt.,  1890,  xv,  521. 

Pinel-Maissonneuve,  I^.;  Bull,  et  Mem.  Soc.  Med.  des  Hup.,  1891,  viii,  137;  Bull,  et  Mem. 
Soc.  Franc.  d'Ophthal.,  1891,  ix,  310;  Archives  d'Ophtalmologie,  July-August,  1891,  p.  309. 

Pineles,  F.:  "Akromegalie  und  Diabetes  M.eWitxxs,"  Jahrbuch  der  Wiener  k.  k.  Kranli., 
1897,  Bd.  iv. 

Putnam,  J.  J.:  "Cases  of  Myxoedema  and  Acromegalia  Treated  with  Benefit  with 
Sheep's  Thyroid;  Cachexias  of  the  Thyroid,"  Americaii  Journal  of  the  Medical  Sciences,  1893, 
cvi,  125;  Boston  Medical  and  Surgical  Journal,  Feb.  15,  1894. 


ACROMEGALY  85 

Querenghi  et  Beduschi:  "  Contrib.  alia  casuistica  dell'  acromegalia,"  Annali  de  Otta- 
mologia,  xxvi,  Pavia. 

Rake,  Bevan:  British  Medical  Journal,  1893,  i,  51S. 
Rampoldi,  V.:  Gazz.  Med.  Lojnb.,  Milano,  1894,  liii,  loi. 
Ransom,  W.  B.:  British  Medical  Jourtial,  1895,  i,  1259. 

Rath:  Ein  Beitrag  zur  Casuistik  der  Hypophysistumoren,  Gottingen,  1888;  Grae/e's 
Archivf.  Oph.,  xxxiv,  1888. 

Rath:  Ein  Beitrag  zur  Casuistik  der  Hypophysistumoren,  Gottingen,  1S8S. 
Rauzier,  G.:   Mo7itpelier  Med.  Supp.,  1893,  ii,  623;    "Diagnosis   from   osteo-arthropathy 
pneiimique,"  Rev.  de  Med.,  ii,  1891,  p.  56. 

Recklinghausen,  Von:   Virchow' s  Arch.  f.  Path.  Anat.,  1S90,  cxix,  36. 
Redmond:  Dublin  Journal  of  Medical  Science,  January,  1891. 
Regnault:  Revue  Neurologique,  Feb.  28,  1898. 

Reimar,  M.:  "Ein  Fall  von  Amenorrhea  bei  Acromegalie,"  Halle  Dissert.,  1893. 
Remington,  F.:  Tr.  Med.  Soc.  New  York,  1894,  266. 
Renner:   Vereinsbl.  d.  Pfals.  Aerzte,  Frankenthal,  1890,  vi,  164. 
Rieder:  Miinchener  Med.  JVoch.,  1893,  p.  391. 
Riegel:  Deutsche  Med.  IVoch.,  1S93,  p.  776. 

Rogowitsch,  N.:  "  Die  Veranderungen  derHypophyse  nach  Entfernungder  Schildruss," 
Beitr.  z.  Path.  Anat.  v.  Zeigler,  1889,  Bd.  iv;  "Zur  Physiologie  der  Schildnise,"  Centralb.f.  d. 
Med.  IVoch.,  1886,  p.  530;  "  Sur  les  effets  de  I'ablation  du  corps  thyroide  chez  les  animaux," 
Arch,  de  Physiologie,  1888,  Bd.  ii,  p.  419. 

RoUeston,  H.  D.:  British  Medical  Journal,  1890;  Lancet,  April  25,  1896,  and  1897,  ii,  p.  1190; 
"Treatment  of  Acromegaly  by  Extracts  of  Thyroid  and  Pituitary  Glands,"  Lancet,  Dec.  4, 
1897,  p.  1443. 

Ross:  International  Clinics,  vol.  i,  1891. 
Ross  and  Bury:  (Post-mortem  notes),  Lancet,  1891,  i,  1383. 
Roth,  V.  K.:  Med.  Obozr.  Mosk.,  1892,  xxxviii,  561. 
Roth:   Virchow^s  Archiv,  1889. 

Rothmell,  J.  R.:  Journal  of  the  American  Medical  Association,  March  20,  1897.   (Autopsy.) 
Ruttle:   Medical  Press  and  Circular,  I^ondon,  1891;   British  Medical  Journal,  March  28, 
1891,  p.  697. 

Sacchi,  E.;  Riv.  Veneta  di  Sc.  Med.,  Venezia,  1889,  xi,  417. 
Sacchi  and  Vassali:  Centralbl.f.  Allgem.  Path.  Anat.,  May,  1894. 

Salbey,  M.:  "Ein  Fall  von  Sogenannter  Akromegalie  mit  Diabetes  Mellitus,"  Erlangen, 
1889,  Thesis,  Mihich.  Med.  IVoch.,  1889. 

Sarbo,  A.:  Orvosi  heti,  Budapest,  1892,  136,  149;  Pest.  Med.-Chir.  Presse,  Budapest,  1892, 
xxxviii,  575. 

Saucerotte:  Melanges  de  Chirurgie,  i8or,  Part  i,  p.  407;  referred  to  in  Revue  de  Medecine, 
tome  vi,  1886,  p.  316. 

Saundby,  R.:  Illustrated  Medical  News,  London,  18S9,  ii,  195. 
Schaefer  and  Oliver:  Journal  of  Physiology,  1895,  p.  277. 
Schaposchnikoff,  B.  M.:  Med.  Obozr.  Mosk.,  1889,  xxxii,  865. 

Schiff,  A.:  "Ablation  of  the  Thyroid,"  Rev.  Med.  de  la  Suisse  Rojnande,  Feb.  and  Aug., 
1884;  "Influence  of  Thyroid  and  Pituitary  Glands  on  Metabolism,"  Wiener  Klin.  Woch., 
March  25,  1897. 

Schlesinger,  H.:    "Treatment  by  Mercury,"  La  Semaine  Medicate,  1S95,  p.  51;   Wiener 
Med.  P-esse,  1895,  p.  186;  Two  Cases,  Neurologisches   Centralbl.,  xiii,  1894,  p.  741;  "Partielle 
Acromegalie,"  Wiener  Klin.  Woch.,  1897,  p.  445;  Neurologisches  Centralbl.,  1894,  p.  741. 
Schmidt:  "  Skiagraphs  of  Acromegaly,"  Medicine,  p.  549,  1897. 

Schultze,  F.:  Deutsche  Med.  Woch.,  1889,  xv,  981,  and  1896,  p.  407;  Deutsche  Zeitschr.  f 
Nervenheilk.,  11  Band,  i  and  2  Heft,  1S97;  Fourteenth  Congress,  etc.,  Wiesbaden,  1S96. 
Schwartz:  St.  Petersb.  Med.  Woch.,  1890. 

Schwoner,  J.:  "  Ueber  hereditare  Akromegalie,"  Zeit.f.  Klin.  Med.,  xxxii,  Supp.,  p.  202. 
Sears,  G.  G.:  Lancet,  1896,  vol.  ii,  p.  614;  Boston  Medical  and  Surgical  Journal,  July  2,  1S96. 
Shiach,  S.  A.:  Lancet,  1893,  iii  369- 

Sigurini  et  Caporiacco:  Riforma  Medica,  1895,  xi,  107. 

Silcock  and  Campbell:  Two  Cases,  Trans.  Clinical  Society  of  London,  vol.  xxiii,  1S90. 
Silva:  "Caso  di  acromegalia  con  atrophia  dei  testicoli,"  La  Riforma  Med.,  1895,  ii,  532. 
Snell:  British  Medical  Journal,  1S95,  ii,  p.  950. 
SoUier:  France  Med.,  1S89. 

Somers:  Occidental  Medical  Times,  Sacramento,  California,  October,  1891. 
Souques:  "  Maccus,  polichinelle  et  I'acromegalie,"  Nouvelle  Iconographie  dela  SalpHrih-e, 
No.  6,  1896. 


86  ACROMEGALY  •• 

Souques  et  Gasne:  Nouv.  Iconog.  de  la  Salpitriere,  1892. 

Souza-IyCite,  J.  D.:  Essay,  Paris,  1890. 

Spillmann,  P.,  and  Haushalter:  Rev.  de  Med.,  Paris,  1891,  xi,  775. 

Squance,  T.  C:  "Notes  on  a  Post-mortem  Examination,"  British  Medical  Journal,  1893, 

ii,  993- 

Steinhaus:  Mem.  de  la  Soc.  de  Med.  de  Varsovie,  1895,  iv,  p.  953. 

Stembo:  St.  Petersburg  Med.  JVoch.,  1891,  Nos.  45  and  46. 

Sternberg,  M.:  Zeitschr.  fur  Klin.  Med.,  Berlin,  1895,  xxvii,  86,  150;  NolhnageVs  Specielle 
Pathologie,  Bd.  vii,  p.  116,  Vienna,  1897;  Neurologisches  Centralbl.,  xiii,  1894,  p.  742. 

Stieda:  "  Ueber  das  Verhalten  der  Hypophyse  des  Kaninchens  nach  entfernung  der 
Schildruse,"  Dissert.,  Konigsberg,  1890;   Ziegler's  Beitrage  z.  Path.  Anat.,  1890,  Bd.  vii,  p.  537. 

Stroebe:  Centralbl.  f.  Pathologie,  vi,  1895,  p.  721. 

Striimpell:  Munch.  Med.  JVoch.,  Aug.  15,  i88g;  Neurologisches  Centralblatt,  1894,  p.  506; 
Deutsch.  Zeitschr.  f.  Nervenheilk.,  11  Band,  i  and  2  Heft,  1897. 

Strzeminski,  J.:  "Troubles  oculaires  dans  I'acromegalie "  (three  cases).  Archives 
d'Ophtalmologie,  Paris,  February,  1897. 

Surmont,  H.:  "Acromegalic  a  debut  precoce,"  N.  Iconogr.  de  la  SalpHriire,  1890,  iii,  147. 

Swanzy,  H.  R.:  "Defective  Vision  and  Other  Ocular  Derangements  in  Cornelius 
Magrath,  the  Irish  Giant,"  Proc.  Royal  Irish  Academy,  Dec.  10,  1894. 

Szymonowicz:  "  Experiments  with  hypophysis  cerebri,"  Pfluger's  Archiv,  1896. 

Tamburini,  A.:  Centralbl.  f.  Nervenheilk.,  1894,  v,  625;  Revue  Neurologique,  November, 
1897. 

Tanzi,  E.:  Riv.  Clin.,  Milano,  1891,  xxx,  533. 

Taruffi:  "  Caso  Delia  Macrosomia,"  Annali  Univers.  di  Med.,  1879,  t.  247;  Reale  Acad,  dell' 
Instituto  di  Bologna,  tome  x,  1879,  p.  63. 

Thayer,  W.  S.:  "  Hypert.  Pul.  .Osteo-arthropathy,"  New  York  Medical  Journal,  Jan.  11, 
1896;  Philadelphia  Medical  Journal,  1898,  ii. 

Thomas,  J.  Lynn:  British  Medical  Journal,  April  11,  1896;  ibid.,  June  i,  1895,  p.  909. 

Thomas:  Rev.  Med.  de  la  Suisse  Romande,  Geneve,  1893,  xiii,  362. 

Thomson,  H.  A.:  "Description  of  an  Acromegalic  Skeleton,"  yowrwa/  of  Anatomy  and 
Physiology,  London,  1889-90,  xxiv,  475. 

Thorne,  Lesley  Thorne:  British  Medical  Journal,  March  14,  1896;  Lancet,  1896,  i,  771. 

Tikomiroff:  "Vascular  Changes  in  Acromegaly,"  Presse  Medicate,  No.  70,  Aug.  26,  1896; 
Rev.  Neurologique,  1896,  p.  310. 

Von  Torday:  "Congenital  Giant  Growth  of  the  Extremities,"  yaAriwcA  /.  Kinderheil- 
kunde.  Bd.  xliii.  Heft  i,  1896. 

Tresilian:  "  Myxcedema,"  British  Medical  Journal,  March  24,  1888,  p.  642. 

Tschisch:  Deutsch.  Petersb.  Med.  JVoch.,  1891. 

Uhthoff:  "Sehstorungen,"  etc.,  Berliner  Klin.  JVoch.,  1897,  p.  461. 

Unna  und  Mendel:  Mu7ich.  Med.  JVoch.,  Dec.  3,  1895. 

Unverricht:  "Akromegalie  und  Trauma,"  Munch.  Med.  JVoch.,  1895,  xiii,  302,  329. 

Valat:  Gaz.  d.  Hop.,  1893,  Ixvl,  1209. 

Vassali:  (See  Sacchi.) 

Verga:  "  Caso  singolare  de  prosopectasia,"  Rendicont.  del  Reale  Inst,  de  Scienze  e  Letter e, 
April  28,  1864. 

Verstraeten,  C:  Rev.  de  Mid.,  1889,  ix,  377. 

Vinke,  H.  H.:  Medical  Record,  1896,  ii,  p.  779. 

Virchow,  R.:  "  Ein  Fall  und  ein  Skelet  von  Akromegalie,"  Berl.  Klin.  JVoch.,  1889,  xxvi, 
81;  Deutsche  Med.  JVoch.,  1889,  xv,  73;  Illustrated  Medical  News,  London,  1889,  ii,  241. 

Wadsworth:  Boston  Medical  and  Surgical  Journal,  Jan.  i,  1885. 

Waldo,  H.:  British  Medical Jouriial,  1890,  i,  662. 

Wells,  H.  Gideon:  "The  Thyroid  Gland  and  its  Congeners," /owrwa/  of  the  American 
Medical  Associatio7i,  1897,  p.  1009. 

Whyte,  J.  M.:  Lancet,  1893,  i,  642. 

Wilks:  Clin.  Soc.  London,  April  13,  1888. 

Wolf,  Kurt:  Beitrdge  zur  Path.  Anat.,  u.  s.  w.,  Zeigler,  xiii,  p.  629. 

Worcester,  W.  L.:  "Case  of  Acromegaly  with  Autopsy,"  Boston  Medical  and  Surgical 
Joiirnal,  April  23,  1896. 

Yamasaki,  J.:  Kyoto  Igakkwai Zashi,  1893,  No.  72. 

Zeigler,  Ernst;  Lehrbuch  der  Allgemeine  Pathologie,  u.  s.  w.,  Band  i. 


NDEX 


Abdomen 

Acromegaly 55, 

Age 

Albuminuria 20, 

Amenorrhea 

Anatomy 

Andriezen 

Animal  extracts 

Apoplexj' 

Appetite  increased 

Arnold 40, 

Arteries 

Arthritis 

Blood 

Bones 11, 

Boyce 

Brown-Sequard 

Cardiac  palpitation 

Cerebellum 

Chin 

Circulatory  organs 

Costanzo 

Course  and  duration 

Cunningham 

Dallemagne 

Dana,  C.  I, 

Depression 

Development,  premature 

Diabetes 20, 

Diagnosis 

Electrical  reactions 

Elephantiasis 

Embryology 

Epistaxis 

Erb's  sign  (thymus) 

Etiology 

Exophthalmic  goitre 15, 

Exophthalmus 

Family  form 

Feet 

Fingers 

Foamier 

Freund 

Genital  organs 

Giant  skeleton 

Gigantism 

Glioma 

Graves'  disease 

Hair 

Hagner  Brothers 40, 

Hands 

Headache 5, 

Hearing 

Hemianopsia 

Heredity 

Hutchinson,  Jonathan 

Hutchinson,  Woods 


14        Hypophysis 32 

66  Hypophysis  in  myxedema 15 

44  Irish  Giant 50 

67  Joints 18 

22  Keen 22 

31  Knee-jerk 18 

33        Kyphosis 11 

59        I^arynx 15 

29  lyips 8 

27       Macrosomia i 

43        Mammse 16 

16        Marinesco 28,  61,  63 

45  Massalongo 47 

21        Megalacria i 

42  Mitchell,  S.  W.  (case  of  aneurism) 39 

32  Muscles 18 

59  Myxedema 15,  55 

27  Myxedema,  diagnosis 15 

28  Nails 5,  20 

II        Neck 12 

16        Nervous  system 28 

60  Neurosis,  trophic 46 

30  Nose 8 

50        Ocular  symptoms 22 

47  Operative  treatment 65 

13        Optic  atrophy 26 

27        Osteitis  deformans 56 

53  Ott's  experiments 63 

67        Pachyacria i 

54  Pain 29 

18        Paraplegia 28 

56        Pathology 35 

33  Paresthesia 29 

31  Pituitary  body 31 

15  Pituitary'  extract 61 

43  Pituitary  fossa 50 

50        Prognathism 10 

23  Psychic  symptoms 27 

43  Pulmonary     hypertrophic     osteo- arthro- 

10  pathy 55 

5        Pupils 23 

16  Race 44 

48  Rauzier 55 

16        Reflexes 18 

69        Respiratory  organs 16 

50        Rheumatism 56 

29  Rogowitsch 33 

15        Rolleston 49 

20  Roentgen  photography 7,  57 

43        Sarbo's  case 40 

5        Sarcoma  of  hypophysis 37 

21  Sensation 21 

27        Sex 44 

24  Sexual  desire 22 

43        Skiagraphy 7,  57 

53        Skin 20 

52        Special  senses 27 

87 


INDEX 


Spinal  cord  and  brain 42 

Spine II 

Sternberg's  table  of  sj'inptoms 29 

Strabismus 23 

Symptomatology 3 

Syringomyelia 28 

Tachj'cardia 16 

Tamburini 47 

Teeth 8 

Temperature 21 

Tetranopsia 24 

Theories 45 

Thirst 27 


Thymus 15,  40 

Thyroid 13,  40 

Thyroid  extract 59 

Tinnitus  aurium 27,  29 

Tongue 8 

Trauma 44 

Treatment 57 

Tremor 18 

Tumors  of  the  h3^pophysis 38 

Urine 20 

Varicose  veins 16 

Vision 23 


W 


